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Persistent racial disparities in health outcomes have catalyzed legislative reforms and heightened scientific focus recently. However, despite the well-documented properties of skin pigments in binding drug compounds, their impact on therapeutic efficacy and adverse drug responses remains insufficiently explored. This perspective examines the intricate relationships between variation in melanin-based skin pigmentation and pharmacokinetics and -dynamics, highlighting the need for considering diversity in skin pigmentation as a variable to advance the equitability of pharmacological interventions. The article provides guidelines on the selection of New Approach Methods (NAMs) to foster inclusive study designs in preclinical drug development pipelines, leading to an improved level of translatability to the clinic.

Aposematic organisms rely on their conspicuous appearance to signal that they are defended and unpalatable. Such phenotypes are strongly tied to survival and reproduction. Aposematic colors and patterns are highly variable; however, the genetic, biochemical, and physiological mechanisms producing this conspicuous coloration remain largely unidentified. Here, we identify genes potentially affecting color variation in two color morphs of Ranitomeya imitator: the orange-banded Sauce and the redheaded Varadero morphs. We examine gene expression in black and orange skin patches from the Sauce morph and black and red skin patches from the Varadero morph. We identified genes differentially expressed between skin patches, including those that are involved in melanin synthesis (e.g. mlana, pmel, tyrp1), iridophore development (e.g. paics, ppat, ak1), pteridine synthesis (e.g. gch1, pax3-a, xdh), and carotenoid metabolism (e.g. dgat2, rbp1, scarb2). In addition, using weighted correlation network analysis, we identified the top 50 genes with high connectivity from the most significant network associated with gene expression differences between color morphs. Of these 50 genes, 13 were known to be related to color production (gch1, gmps, gpr143, impdh1, mc1r, pax3-a, pax7, ppat, rab27a, rlbp1, tfec, trpm1, xdh).

Excessive ultraviolet (UV) radiation can cause human skin erythema, tanning, inflammation and other adverse reactions. Human skin can spontaneously synthesize endogenous melanin under UV radiation to defend against the damage of UV, but skin problems such as light damage and light aging cannot be avoided due to its low UV shielding efficiency. Therefore, we design a natural and biocompatible PGDA (poly-γ-glutamic acid/melanin-like hydrogel) sunscreen hydrogel by crosslinking melanin-like L -lysine-doped polydopamine (PDA- L) and amino acid biopolymer poly-γ-glutamic acid, which displays good biosafety, efficient UVA shielding performance and excellent anti-inflammatory performance in the applications of skin protection from the sun and repair after sunburn. The introduction of PDA- L to the hydrogel can improve the absorption intensity in the UV region and the antioxidative performance of the hydrogel. Meanwhile, the usage of biocompatible PGDA sunscreen hydrogel can avoid the skin oxidative damage and penetrative toxicity of conventional sunscreens. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment. [ABSTRACT FROM AUTHOR]

Background: Microbial melanins possess a broad spectrum of biological activities. However, there is little understanding of their neuroprotective and neuronal cell differentiation properties. This study aimed to extract, purify, and modify melanins from two medicinal fungi (Daedaleopsis tricolor and Fomes fomentarius), and to evaluate their antioxidant activity, as well as their cell protective ability against neurotoxins. In addition, the study also investigated the feasibility of combining melanins or modified melanins with retinoic acid (RA) to induce neuronal differentiation. Methods: Melanin was extracted and purified using alkaline acid-based methods. Antioxidant activities and neuroprotective effects were evaluated using the DPPH (1,1-diphenyl-2-picrylhydrazyl) and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assays, respectively. In addition, morphological changes of SH-SY5Y cells were recorded by using a Pannoramic MIDI scanner. Results: All melanins and arginine-modified melanins displayed mild DPPH scavenging activities, which were statistically lower than that of ascorbic acid (p < 0.05). In terms of neuroprotection, both melanins and arginine-modified melanins exhibited significant cell protection against H2O2 after 24 h exposure (p < 0.05). Notably, there is no significant difference between F. fomentarius melanin and its modified form as they both increased cell viability by about 20%. Contrarily, while D. tricolor melanin enhanced the cell viability with 16%, its modified form increased the cell viability with 21%. These activities, however, are significantly lower than the positive control (N-acetylcysteine, p < 0.05). Regarding MPTP, only the arginine-modified melanins of the two fungi significantly protected the cells after 24 h exposure to the toxin (p < 0.05). Specifically, F. fomentarius and D. tricolor modified melanins enhanced the cell viability with 10.2% and 11.1%, respectively, whereas that of the positive control was 13.2%. Interestingly, combining RA (10 µM) with 20 µg/mL of either F. fomentarius, or especially D. tricolor arginine-modified melanin, significantly promoted neuroblastoma cell differentiation into mature neuronal cells compared to using RA alone (p < 0.05). Conclusions: The arginine-modified melanins of D. tricolor and F. fomentarius have potential for neuroprotection against Parkinsonian neurotoxins. In addition, the arginine-modified melanin of D. tricolor may serve as an excellent material for research in neuroblastoma treatment. [ABSTRACT FROM AUTHOR]

Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%–90% as effective as VEGF in the stimulation of neovascularization in in vitro models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson's trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%–90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established. [ABSTRACT FROM AUTHOR]

Pyomelanin, a polymeric pigment in Pseudomonas, arises mainly from alterations in tyrosine degradation. The chemical structure of pyomelanin remains elusive due to its heterogeneous nature. Here, we report strain‐specific differences in pyomelanin structural features across Pseudomonas using PAO1 and PA14 reference strains carrying mutations in hmgA (a gene involved in pyomelanin synthesis), a melanogenic P. aeruginosa clinical isolate (PAM), and a melanogenic P. extremaustralis (PexM). UV spectra showed dual peaks for PAO1 and PA14 mutants and single peaks for PAM and PexM. FTIR phenol : alcohol ratio changes and complex NMR spectra indicated non‐linear polymers. UVC radiation survival increased with pyomelanin addition, correlating with pigment absorption attenuation. P. extremaustralis UVC survival varied with melanin source, with PAO1 pyomelanin being the most protective. These findings delineate structure‐based pyomelanin subgroups, having distinct physiological effects. [ABSTRACT FROM AUTHOR]

Congenital melanocytic nevi (CMN) are pigmented lesions present at birth, varying widely in size and clinical impact. In rare instances, these nevi become visible during the first months of life, a phenomenon known as tardive melanocytic nevi (tardive CMN). Giant congenital melanocytic nevi (GCMN) are defined as nevi larger than 40 cm in projected adult size (PAS). Their association with the central nervous system (CNS) poses significant risks, including melanoma and neurocutaneous melanocytosis (NCM), where melanocytes infiltrate the CNS, potentially causing seizures, hydrocephalus, and, rarely, CNS melanoma. MRI is recommended for GCMN patients, particularly those with numerous satellite nevi or neurological symptoms, to detect CNS involvement. The Nevosurgery Network recommends MRI examinations in cases of GCMN (>40 cm PAS), the presence of over 20 concomitant nevi, and neurological symptoms requiring clarification. CMN can be associated with melanocyte accumulations and melanin deposits in the brain, spinal cord, and leptomeninges. [ABSTRACT FROM AUTHOR]

Background: The picosecond 755‐nm alexandrite laser and topical tranexamic acid (TA) have shown promise in treating melasma. Aim: This aim of this study was to evaluate the efficacy and safety of combining to a picosecond 755‐nm alexandrite laser combined with topical TA for melasma treatment. Patients and Methods: Forty‐eight patients' facial halves with bilateral symmetrical melasma were randomized to receive either topical TA and picosecond laser treatment or laser monotherapy. All patients received three consecutive picosecond laser treatment sessions at 4‐week intervals, and additional one side facial received topical TA treatment twice daily until 4 weeks after the third treatments. Efficacy was assessed using the Modified Melasma Area and Severity Index (mMASI) score, VISIA (Canfield, USA) red area feature counts, and average pore volume as measured by Antera 3D®. Patient satisfaction was evaluated through questionnaires. Results: Thirty‐five patients completed the study. Post‐treatment, mMASI scores and VISIA red area feature counts were lower in combination therapy halves and laser monotherapy halves, and average melanin level was lower in the combination therapy halves (p < 0.05). Comparisons between the combination therapy halves and laser monotherapy halves after the third treatment revealed significant differences in mMASI scores, melanin levels, and VISIA red area feature counts (p < 0.05). After treatment, patient satisfaction rates in the combination therapy halves and monotherapy halves was 71.4% and 54.3%, respectively (p < 0.05). No obvious adverse effects were observed in the combination therapy halves; whereas, 10.42% (5/48) of participants in the laser monotherapy halves experienced temporary pigmentation, which resolved within 3 months. Conclusion: The picosecond 755‐nm alexandrite laser, when used independently and in combination with topical TA, has been proven to be effective in the improvement of melasma. However, the combined treatment approach showed a more pronounced improvement in melasma symptoms, with higher patient satisfaction, and was associated with a lower incidence of adverse effects. These findings strongly support that integrating topical TA with picosecond laser therapy as a superior therapeutic strategy for melasma management. Clinical Trial Registration: Chinese Clinical Trial Registry: ChiCTR2200057771. [ABSTRACT FROM AUTHOR]

Melanin, particularly eumelanin, is commonly viewed as an efficient antioxidant and photoprotective pigment. Nonetheless, the ability of melanin to photogenerate reactive oxygen species and sensitize the formation of cyclobutane pyrimidine dimers may contribute to melanin‐dependent phototoxicity. The phototoxic potential of melanin depends on a variety of factors, including molecular composition, redox state, and degree of aggregation. Using complementary spectroscopic and analytical methods we analyzed the physicochemical properties of Dopa‐melanin, a synthetic model of eumelanin, subjected to oxidative degradation induced by aerobic photolysis or exposure to 0.1 M hydrogen peroxide. Both modes of oxidative degradation were accompanied by dose‐dependent bleaching of melanin and irreversible modifications of its paramagnetic, ion‐ and electron‐exchange and antioxidant properties. Bleached melanin exhibited enhanced efficiency to photogenerate singlet oxygen in both UVA and short‐wavelength visible light. Although chemical changes of melanin subunits, including a relative increase of DHICA content and disruption of melanin polymer induced by oxidative degradation were considered, these two mechanisms may not be sufficient for a satisfactory explanation of the elevated photosensitizing ability of the bleached eumelanin. This study points out possible adverse changes in the photoprotective and antioxidant properties of eumelanin that could occur in pigmented tissues after exposure to high doses of intense solar radiation. [ABSTRACT FROM AUTHOR]

Albinism is a result of cells that are unable to make melanin or pigments which are necessary to color the skin. It occurs very rarely in the wild animal. Although several species of monkeys with albino individuals have been recorded in other parts of the world, it has never been recorded in Grey Langur and endemic Toque Macaque. Hence this would be the first ever albino Grey Langur and endemic Toque Macaque individuals recorded in Sri Lanka. [ABSTRACT FROM AUTHOR]

Melanins are macromolecular pigments widely spread in many living organisms, with unique physical and chemical properties. Specifically, their conductive properties have drawn attention for applications in different devices; however, the electrochemical response is equally necessary for designing technologies in sustainable bioelectronics. In this sense, we report a comparative study of the redox electrochemical properties of non‐functionalized and sulfonated melanins in different pH environments. The electrochemical response was investigated using cyclic voltammetry, electrochemical impedance spectroscopy, dielectric permittivity and AC/DC conductivity at pH 3, 5 and 7. The voltammetric currents were higher at low pH, in agreement with the known proton transport properties of melanins. The effect of pH on electrochemical properties was slightly more significant in non‐functionalized pigments. Melanins with a higher 5,6‐dihydroxyindole carboxylic acid/5,6‐dihydroxyindole ratio showed high DC current and low impedance. No significant difference was observed in the dielectric relaxation process between the different samples. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: Body color is a prominent phenotypic trait and a significant economic characteristic in fish. While current research mainly examines the effects of genetic factors, less emphasis has been placed on the role of endogenous hormones in fish body color. Methods: In this study, we investigated the changes in phenotype and pigment content in juvenile Sinibrama taeniatus after a 30-day treatment with gradient concentrations of L-thyroxine. To further understanding of the regulatory roles of thyroid hormone on pigment synthesis, we investigated the expression changes in genes involved in melanin-based and non-melanin-based pigmentation under the different hormonal regimes. Results: Compared to the control group, the body color of the low-concentration L-thyroxine treatment group (20 nM) was lighter, while that of the highconcentration group (40 nM and 80 nM) was darker. Thyroid hormone treatment simultaneously affected melanophores, xanthophores, and iridophores in different ways, leading to an increase ofmelanin and guanine, and a reduction of pteridine and β-carotene. These findings suggest that thyroid hormone regulates fish body color pigment synthesis through both melanin-based and non-melanin-based mechanisms. Additionally, expression of genes involved in melanin-based (e.g. ctnnb1, wnt10b, and adcy3) and non-melanin-based pigmentation (e.g. xdh, ltk, pnp4a, and mpv17) weremodified by thyroid hormone treatment. Discussion: Our results enhanced the understanding of the role of thyroid hormone in fish pigmentation and provide useful information for cultivating fish with desirable body colors in aquaculture. [ABSTRACT FROM AUTHOR]

ABSTRACT Recent studies underscore the beneficial impacts of oral natural plant extracts on human skin health, though clinical evidence of their efficacy and safety is limited. This study evaluates the skin health effects of a novel oral supplement containing Rosa roxburghii, Punica granatum, and rose extracts (RPR) 0.70 healthy female participants were randomly assigned to either a control group or an RPR group, with the latter ingesting 20 mL of the RPR supplement daily on an empty stomach over 8 weeks. After 8 weeks, the RPR group exhibited significant enhancements (p < 0.001) in skin hydration, glossiness, elasticity, and skin tone, with increases of 69.02%, 30.48%, 25.97%, and 7.52%, respectively. Concurrently, decreases in skin firmness and melanin levels were observed at 21.17% (p = 0.007) and 25.06% (p < 0.001), respectively. Statistical analysis confirmed that these changes were significantly greater than those in the control group. Image analysis indicated no significant changes in mean optical density of hyperpigmented spots within the RPR group (p = 0.367), but a significant reduction in the areas of hyperpigmented spots, under‐eye fine lines, and crow's feet by 41.50%, 37.55%, and 29.36%, respectively (p < 0.001), whereas no significant changes were detected in the control group. Importantly, no adverse effects were observed. These findings suggest that the combined intake of Rosa roxburghii, Punica granatum, and rose extracts can improve skin health, offering a promising natural alternative for dermatological care. [ABSTRACT FROM AUTHOR]

Elsinoë species are phytopathogenic fungi that cause serious scab diseases on economically important plants. The disease symptoms arise from the effects of a group of phytotoxins known as elsinochromes, produced via a type-I polyketide synthase (PKS) biosynthetic pathway. The elsinochrome gene cluster was first annotated in Elsinoë fawcettii where the main type-I PKS gene was characterized as EfPKS1. A later study showed that this gene and the associated cluster had not been correctly annotated, and that EfPKS1 was actually the anchor gene of the melanin biosynthetic pathway. A new type-I PKS gene EfETB1 associated with elsinochrome production was also identified. The aim of this study was to identify all type-I PKS genes in the genomes of seven Elsinoë species with the goal of independently verifying the PKS containing clusters for both melanin and elsinochrome production. A total of six type-I PKS classes were identified, although there was variation between the species in the number and type of classes present. Genes similar to the E. fawcettii EfPKS1 and EfETB1 type-I PKS genes were associated with melanin and elsinochrome production respectively in all species. The complete melanin and elsinochrome PKS containing clusters were subsequently annotated in all the species with high levels of synteny across Elsinoë species. This study provides a genus-level overview of type-I PKS distribution in Elsinoë species, including an additional line of support for the annotation of the melanin and elsinochrome PKS containing clusters in these important plant pathogens. [ABSTRACT FROM AUTHOR]

Simple Summary: Animal models are crucial for exploration of the causes of and potential treatments for squamous cell carcinoma, a common type of skin cancer. This study compared four different hairless mouse models to determine which is most suitable for studying skin cancer development when exposed to ultraviolet (UV) light. The models varied in their skin characteristics, such as the presence of melanin, cholesterol level, and immune system function. By monitoring various skin health parameters and analyzing proteasome activity, this study found that the SKH-hr2+ApoE and SKH-hr2 models were the most effective for further research into squamous cell carcinoma. In contrast, the SKH-hr1 model, despite its common use, was less suitable. These findings will help guide future research efforts in understanding and developing treatments for skin cancer. Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis. [ABSTRACT FROM AUTHOR]

Four new alkylamides named retroframides A-D (1-4) together with twenty-two known compounds were isolated from the fruits of Piper rectrofractum. The structures of new compounds were elucidated on the basis of spectroscopic data including 2D NMR and chemical derivatization followed by GC-MS analysis. Of isolated compounds, piperine (25) and pellitorine (26) revealed moderate inhibition against tyrosinase with percentage inhibition of 36.1 and 40.7. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the effect of ionising and ultraviolet radiation on stimulating melanin secretion in Tetrahymena pyriformis. Cell cultures were exposed to different doses of radiation for 48, 72 and 96 h. After incubation, melanin was extracted and analysed. Our results showed that melanin concentration increased with increasing irradiation dose and exposure duration. Melanin was insoluble in water and organic solvents but soluble in alkaline and acidic solutions. A linear correlation between the logarithm of melanin absorbance and wavelength ranging from 400 to 600 nm was observed. The HPLC chromatograms of melanin degradation products by the alkaline hydrogen peroxide oxidation method revealed the existence of four peaks. The natural melanin standard extracted from the cuttlefish Sepia officinalis was used as a reference compound of eumelanin markers. These markers were detected in control cells, irradiated cells and black human hair but with different intensities. [ABSTRACT FROM AUTHOR]

Background: Skin tone assessment is critical in both cosmetic and medical fields, yet traditional methods like the individual typology angle (ITA) have limitations, such as sensitivity to illuminants and insensitivity to skin redness. Methods: This study introduces an automated image‐based method for skin tone mapping by applying optical approaches and deep learning. The method generates skin tone maps by leveraging the illuminant spectrum, segments the skin region from face images, and identifies the corresponding skin tone on the map. The method was evaluated by generating skin tone maps under three standard illuminants (D45, D65, and D85) and comparing the results with those obtained using ITA on skin tone simulation images. Results: The results showed that skin tone maps generated under the same lighting conditions as the image acquisition (D65) provided the highest accuracy, with a color difference of around 6, which is more than twice as small as those observed under other illuminants. The mapping positions also demonstrated a clear correlation with pigment levels. Compared to ITA, the proposed approach was particularly effective in distinguishing skin tones related to redness. Conclusion: Despite the need to measure the illuminant spectrum and for further physiological validation, the proposed approach shows potential for enhancing skin tone assessment. Its ability to mitigate the effects of illuminants and distinguish between the two dominant pigments offers promising applications in both cosmetic and medical diagnostics. [ABSTRACT FROM AUTHOR]

Vascular anomalies can be broadly classified as vascular tumors or vascular malformations, depending on the degree of endothelial involvement. These lesions can be subtle and challenging to diagnose in individuals with darker skin tones, which can lead to a delay in treatment. Improving diagnostic accuracy of these lesions may prevent progression and potential adverse outcomes when left untreated. Here, we present a review of common vascular anomalies with a focus on diagnostic considerations in individuals with skin of color. [ABSTRACT FROM AUTHOR]

The important role of dihydroxynaphthalene-(DHN) melanin in enhancing fungal stress resistance and its importance in fungal development and pathogenicity are well-established. This melanin also aids biocontrol fungi in surviving in the environment and effectively infecting insects. However, the biosynthetic origin of melanin in the biocontrol agents, Metarhizium spp., has remained elusive due to the complexity resulting from the divergence of two DHN-like biosynthetic pathways. Through the heterologous expression of biosynthetic enzymes from these two pathways in baker's yeast Saccharomyces cerevisiae, we have confirmed the presence of DHN biosynthesis in M. roberstii, and discovered a novel naphthopyrone intermediate, 8, that can produce a different type of pigment. These two pigment biosynthetic pathways differ in terms of polyketide intermediate structures and subsequent modification steps. Stress resistance studies using recombinant yeast cells have demonstrated that both DHN and its intermediates confer resistance against UV light prior to polymerization; a similar result was observed for its naphthopyrone counterpart. This study contributes to the understanding of the intricate and diverse biosynthetic mechanisms of fungal melanin and has the potential to enhance the application efficiency of biocontrol fungi such as Metarhizium spp. in agriculture. [ABSTRACT FROM AUTHOR]

Melanin plays an important role in protecting skin cells from harmful UV radiation, but its uneven pigmentation in the skin sometimes demands cosmetic resolution. As a safe and effective way of evening the skin tone, enzymatic decolorization of melanin at the stratum corneum has been proposed. In this regard, the use of lignin peroxidase, in the presence of hydrogen peroxide and veratryl alcohol, an electron mediator, has been explored. Here, we first show that versatile peroxidase (VP) and aryl alcohol oxidase (AAO) purified from the Pleurotus eryngii liquid culture can be used to decolorize melanin without exogenous hydrogen peroxide. This resembles the oxidative degradation pathway of lignin in nature; AAO generates hydrogen peroxide from veratryl alcohol, and VP utilizes generated hydrogen peroxide while using veratryl alcohol as a mediator. We further explored the use of POX_Pe, the crude peroxidase preparation of the Pleurotus eryngii liquid culture, for melanin decolorization because of its better stability. Using POX_Pe and veratryl alcohol, over 60 % of melanin decolorization was obtained in 1 h in the absence of exogenous hydrogen peroxide addition. Furthermore, POX_Pe could decolorize melanin in a 3D human pigmented epidermis model, demonstrating its possible applications in cosmetics. [Display omitted] • Enzymatic decolorization of the skin pigment, melanin, is drawing great attention. • Lignin degrading pathway of Pleurotus eryngii was re-purposed to decolorize melanin. • The system consists of versatile peroxidase and aryl alcohol oxidase. • The crude preparation of the enzymes showed benefits over purified enzymes. • High degree of melanin decolorization in the absence of toxic H 2 O 2 is described. [ABSTRACT FROM AUTHOR]

Dark pigmentation of adults resulting from cold exposure during development is ubiquitous among insects. Yet the costs associated with the developmental plasticity of melanisation have been explored only for a handful of species.We explored two hypotheses relating to colour plasticity of insects. First, if melanin pigments are costly to synthesise and require allocation of resources, increased melanisation should be negatively associated with performance traits (the cost hypothesis). Second, given the positive association between melanisation and immune responses or desiccation resistance in some species, melanisation and performance may co‐vary positively (the positive covariance hypothesis). Furthermore, given the typical differences in reproductive effort and activity between females and males, we expect these performance–melanisation relationships to differ between sexes.We assessed whether temperature‐induced melanisation of the globally invasive beetle Harmonia axyridis f. succinea (Pallas) (Coleoptera: Coccinellidae) was related to standard metabolic rate and flight performance while accounting for developmental temperature and family affiliation.Melanisation explained little variation in standard metabolic rate at most temperatures tested (15, 20, 25, 30 and 35°C). For flight performance and after the cold‐rearing regime, lighter coloured female beetles had increased flight speed compared with darker females, whereas the opposite was found in males. In addition, in warm‐reared beetles, darker individuals had lower mean flight speeds.The results suggest that at least some flight performance costs are associated with developmentally induced melanisation, supporting the cost hypothesis. Disparities in these relationships between males and females suggest that the drivers underlying variation in melanisation differ between sexes. Importantly, variation in melanisation was more acute for females reared in the warm regime compared with equally treated males and to cold‐reared individuals. We propose new directions to test hypotheses pertaining to the maintenance of colour variation and performance between sexes in nature. [ABSTRACT FROM AUTHOR]

Melanin is a high value bioproduct generated through the fermentation of Aureobasidium pullulans, playing a crucial role in various fields, including food, medicine, environmental protection, and materials science. However, its high production costs and low synthetic yields significantly limit its applications. Therefore, it is essential to identify high-yield strains, reduce production costs, and optimize fermentation strategies. In this study, a high melanin-yielding Aureobasidium pullulans 53LC7 was screened and identified, and the fermentation process was optimized based on melanin yield, color value, and pullulan yield. The results indicated that the melanin yield peaked at an initial pH of 6.0, temperature of 27 °C, fermentation time of 6.5 d, and inoculation quantity of 2.5%, achieving a melanin yield of 16.33 g/L. Subsequently, huangjiu lees, a byproduct of huangjiu production, was incorporated into the fermentation medium, resulting in a melanin yield of 5.91 g/L. This suggests that the Aureobasidium pullulans was not effectively utilizing huangjiu lees. To address this, we employed an adaptive evolution strategy, which increased the melanin yield to 8.72 g/L. The enhanced production was correlated with the expression of key genes, including FKS, PKS, and Cmr1. Finally, cellulase was utilized to convert the crude fibers in huangjiu lees, which were difficult to utilize, into usable substrates, while pullulanase was employed to minimize byproduct formation in the fermentation system, resulting in a melanin yield of 19.07 g/L. This study not only provides promising strains for further research but also offers valuable insights for resource production technologies. [ABSTRACT FROM AUTHOR]

ABSTRACT In skin, melanin is synthesized and stored in melanosomes. In epidermal melanocytes, melanosomes are transported to and internalized by the neighboring keratinocytes, subsequently leading to skin pigmentation. Ultraviolet (UV) radiation induces the release of acetylcholine (ACh) from keratinocytes, which in turn activates ACh receptors (AChRs) on nearby melanocytes, forming a proposed “skin synapse”. Here, we illustrated that the UV‐induced melanosome release from cultured B16F10 melanoma cells could be mediated by co‐actions of ACh. In the cell cultures, UV exposure robustly elicited melanosome release. Applied bethanechol (BeCh), an agonist of muscarinic AChR (mAChR), could significantly enhance the release. In parallel, the intracellular Ca2+ mobilization was regulated. The applied antagonists of M1 and/or M3 mAChRs could block the UV‐induced melanosome release and the mobilization of intracellular Ca2+. The phosphorylation of PKC, triggered by UV and BeCh treatments, could be suppressed by the applied mAChR antagonists. The expressions of tethering complex for exocytosis, for example, Sec8, Exo70, and Rab11b, as well as synaptotagmin, were increased under UV exposure together with mAChR agonist: The inductions were fully abolished by M1 or M3 antagonist. Here, we hypothesize that the cholinergic signaling is playing roles in UV‐induced exocytosis of melanosomes. [ABSTRACT FROM AUTHOR]

The first photographic evidence of a leucistic Sloth Bear from Panna Tiger Reserve, Madhya Pradesh, was obtained during a camera trapping survey conducted during 2019-2021. Despite the wide distribution of Sloth Bears in the Indian sub-continent, leucism is extremely rare to find. This record evokes the need for scientific reporting of such encounters and further research on the causal factors of leucism with respect to the species' ecological and conservation implications. [ABSTRACT FROM AUTHOR]

Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of interventions concurrently targeting both inflammation and cancer has encountered significant challenges stemming from various external factors. Herein, a bioactive agent synthesized by genetically engineering melanin‐producing Bacillus thuringiensis (B. thuringiensis) bacteria, simultaneously achieves eco‐friendly photothermal agent and efficient reactive oxygen/nitrogen species (RONS) scavenger benefits, perfectly tackling present toughies from inflammation to cancer therapies. The biologically derived melanin exhibits exceptional photothermal‐conversion performance, facilitating potent photonic hyperthermia that effectively eradicates tumor cells and tissues, thereby impeding tumor growth. Additionally, the RONS‐scavenging properties of melanin produced by B. thuringiensis bacteria contribute to inflammation reduction, augmenting the efficacy of photothermal tumor repression. This study presents a representative paradigm of genetic engineering in B. thuringiensis bacteria to produce functional agents tailored for diverse biomedical applications, encompassing inflammation and cancer therapy. [ABSTRACT FROM AUTHOR]

Tyrosinase is a key enzyme in melanin synthesis, and its natural inhibitors are receiving increasing attention. Rosa × damascena Herrm. essential oil (RDEO), as important functional metabolites, was widely known due to its biological activities. But its tyrosinase inhibitory activity has not been detailed investigated. Therefore, in this paper, RDEO was comprehensively investigated the tyrosinase inhibitory, followed by the phytochemical composition analysis. Activity screening results showed that RDEO exhibited effective anti-tyrosinase activity and was a reversible and mixed-type inhibitor. CD assay results revealed that RDEO could affect the conformation of tyrosinase to reduce the activity. In B16F10 cells, RDEO (25-100 µg/mL) could inhibit intracellular tyrosinase activity and decrease melanin content. Finally, GC-MS analysis of RDEO found that citronellol (21.22%), geraniol (14.1%), eicosane (11.03%), heneicosane (6.65%) and 1-nonadecene (5.16%) were its main phytochemical compositions. This study provided data support for Rosa × damascena Herrm. essential oil as one potential natural tyrosinase inhibitor and its applications in cosmetics and medicine. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusion Hyperpigmentation disorders are caused by the excess production and irregular accumulation of melanin. Existing treatments often have limited efficacy and adverse effects, necessitating the development of new skin‐brightening agents. Lotus sprout extract (LSE) was identified as a potential pigment‐correcting agent. However, the active compounds responsible for driving mechanisms related to this activity remain unknown.This study aimed to investigate the effects of LSE and its active components, neferine and liensinine, on melanin accumulation and to understand how LSE reduces skin pigmentation.Melanin accumulation was analyzed in MNT‐1 human melanoma cells and MelanoDerm human skin equivalents following neferine, liensinine, or LSE treatment. The effects of the compounds on different pathways regulating melanin levels were evaluated by gene expression, biochemical assays, and western blotting. Melanosome ultrastructure was monitored using transmission electron microscopy (TEM).Neferine and liensinine reduced melanin accumulation in MNT‐1 cells without downregulating melanogenesis‐related genes or inhibiting tyrosinase activity. Instead, these compounds increased autophagic flux, suggesting that the reduction in pigmentation was due to increased melanin degradation. LSE also reduced melanin accumulation and activated autophagy in normal human melanocytes and MelanoDerm tissue. Autophagosomes induced by LSE treatment contained only melanosomes, and structural changes in melanosomes suggested that LSE may disrupt melanosome maturation.This study revealed a novel mechanism for LSE, neferine, and liensinine in reducing pigmentation, potentially through the induction of autophagy and subsequent melanosome degradation. These findings suggest that LSE and its enriched bioactive compounds could be promising agents for treating hyperpigmentation. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response. [ABSTRACT FROM AUTHOR]

Background/Objectives: Multiple underlying pathomechanisms may lead to melasma, but there has been no report on the use of optical coherence tomography (OCT) to reveal specific pathomechanisms in individual patients and provide individualized treatments accordingly. Using real-time OCT images, we studied the pathomechanisms of melasma in 12 female patients and the effects of individualized treatments. Methods: Patients were divided into good and bad improved groups according to the improvement in hyperpigmentation at month 4. Results: In the bad improved group, all melanin or confetti melanin had significantly decreased at month 2 or month 4 while granular melanin ratio at month or month 4 significantly increased, the most parameters of dendritic-sharped cells (DCs) before and after treatment were not significantly different, the collagen area or collagen density at month 4 significantly decreased. In the good improved group, there was slightly low all melanin/confetti melanin at month 4 and high granular melanin at month 4 in comparison to the bad improved group. Moreover, most of the parameters in the DCs at month 4 significantly increased while most parameters in collagen at month 4 significantly decreased. Conclusions: OCT is useful in revealing the involved pathomechanisms of melasma in individualized patients. Positive treatment results can be achieved through individualized therapy regimen targeting the pathomechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: Darkness of the pectoral muscles is closely related to the amount of melanin deposited in the muscles of black-boned chickens. Embryonic development is an important stage in muscle melanin deposition. This study used RNA-seq to compare gene expression differences between the pectoral muscles of black-boned and non-black-boned chickens at different developmental periods. The results identified vital genes and EDN3/EDNRB2 signaling pathways involved in melanin deposition via GO and KEGG pathways and WGCNA analyses. Additionally, we identified five specific genes that may regulate melanin deposition in different breeds of black-boned chicken. The pectoral muscle is an important component of skeletal muscle. The blackness of pectoral muscles can directly affect the economic value of black-boned chickens. Although the genes associated with melanogenesis in mammals and birds have been thoroughly investigated, only little is known about the key genes involved in muscle hyperpigmentation during embryonic development. Here, we analyzed melanin deposition patterns in the pectoral muscle of Yugan black-boned chickens and compared differentially expressed genes (DEGs) between the muscles of Wenchang (non-black-boned chickens) and Yugan black-boned chickens on embryonic days 9, 13, 17, and 21. Melanin pigments were found to gradually accumulate in the muscle fibers over time. Using RNA-seq, there were 40, 97, 169, and 94 genes were identified as DEGs, respectively, between Yugan black-boned chicken muscles and Wenchang chickens at embryonic day 9, 13, 17, and 21 stages (fold change ≥2.0, false discovery rate (FDR) < 0.05). Thirteen DEGs, such as MSTRG.720, EDNRB2, TYRP1, and DCT, were commonly identified among the time points observed. These DEGs were mainly involved in pigmentation, melanin biosynthetic and metabolic processes, and secondary metabolite biosynthetic processes. Pathway analysis of the DEGs revealed that they were mainly associated with melanogenesis and tyrosine metabolism. Moreover, weighted gene co-expression network analysis (WGCNA) was used to detect core modules and central genes related to melanogenesis in the muscles of black-boned chickens. A total of 24 modules were identified. Correlation analysis indicated that one of them (the orange module) was positively correlated with muscle pigmentation traits (r > 0.8 and p < 0.001). Correlations between gene expression and L* values of the breast muscle were investigated in Yugan and Taihe black-boned chickens after hatching. The results confirmed that EDNRB2, GPNMB, TRPM1, TYR, and DCT expression levels were significantly associated with L* values (p < 0.01) in black-boned chickens (p < 0.05). Our results suggest that EDNRB2, GPNMB, TRPM1, TYR, and DCT are the essential genes regulating melanin deposition in the breast muscle of black-boned chickens. MSTRG.720 is a potential candidate gene involved in melanin deposition in the breast muscles of Yugan black-boned chickens. [ABSTRACT FROM AUTHOR]

Background: Melanin in the black-bone chicken's body is considered the material basis for its medicinal effects and is an economically important trait. Therefore, improving the melanin content is a crucial focus in the breeding process of black-bone chickens. Luning chickens are black-bone chickens, with black beaks, skin, and meat. To investigate the genetic diversity and molecular mechanisms of melanin deposition in Luning chickens, we conducted whole-genome resequencing to analyze their breeding history and identify candidate genes influencing their black phenotype, along with transcriptome sequencing of dorsal skin tissues of male Luning chickens. Results: Population structure analysis revealed that Luning chickens tend to cluster independently and are closely related to Tibetan chickens. Runs of homozygosity analysis suggested potential inbreeding in the Luning chicken and Tibetan chicken population. By combining genetic differentiation index (Fst) and nucleotide diversity (θπ) ratios, we pinpointed selected regions associated with melanin deposition. Gene annotation identified 540 genes with the highest Fst value in LOC101750371 and LOC121108313, located on the 68.24–68.58 Mb interval of chromosome Z. Combining genomic and transcriptomic data, we identified ATP5E, EDN3, and LOC101750371 as candidate genes influencing skin color traits in black-bone chickens. Conclusions: This study characterized the evolutionary history of Luning chickens and preliminarily excavated candidate genes influencing the genetic mechanism of pigmentation in black-bone chickens, providing valuable insights for the study of animal melanin deposition. [ABSTRACT FROM AUTHOR]

Introduction: Poroid neoplasms (PN) are a heterogeneous group of tumors deriving from sweat glands and folliculo-sebaceous units. Their histological classification and clinical features are challenging. Our aim was to report clinicopathological features of poroid neoplasms. Methods: It is a retrospective study including all cases of poroid neoplasms registered at our Pathology laboratory of Niamey National Hospital (February 2020-February 2024). Results: We registered 13 cases of benign poroid neoplasms: 10 classic poromas (CP) (76.9%), 2 poroid hidradenomas (PH) (15.4%) and 1 dermal duct tumor (DDT) (7.7%). Nine cases (69.2%) had preoperative clinical diagnosis of malignancy. The mean age was 41.1 years (range of 12-70 years) with a slight female predominance. Only 4/13 cases (30.8%) had classical palmoplantar locations. The tumors mean size was 3.7 cm (range of 0.4-8 cm). Clear cells were present in 7 cases (53.8%), apocrine ductal differentiation (mixed or pure) in 6 cases (46.2%), keratin horns in 2 cases (15.4%), squamous eddies in 6 cases (46.2%), melanin pigments in 1 case (7.7%) and sebaceous differentiation in 2 cases (15.4%). Conclusions: Unlike what is classically reported, our study shows that apocrine ductal differentiation, younger age and non-palmoplantar locations are common in poroid neoplasms. [ABSTRACT FROM AUTHOR]

Clearance of comedone is challenging in the treatment of acne, as it is very likely to develop into inflammatory lesions. However, there is lack of effective treatments for dense comedones. Comedone extractor has been widely employed by dermatologists, but the effect is temporary and may cause irritation. CO2 laser is a potential method for dense comedones, but the efficacy and safety need to be explored. In this single-center, randomized, single-blind, self-controlled study, the faces of patients with dense comedones were randomly assigned into two sides receiving either ultra-pulse dynamic CO2 laser or comedone extraction at an interval of 2 weeks for 4 sessions. After 4 treatments, the average comedone reduction rate of the CO2 laser was 64.49%, which was higher than that by the extractor (46.36%) (P <.001). 79.16% of the patients reached over 50% reduction by CO2 laser, while only 37.5% on extractor treated side reached 50% clearance. Texture index, porphyrin index, red zone, erythema index, and transepidermal water loss decreased after both treatments, and CO2 laser showed more improvement. There was no difference in hydration index and melanin index between the two treatments. No permanent or severe side effects were observed on both sides. The CO2 laser showed higher comedone clearance with lower pain scores than the comedone extractor. [ABSTRACT FROM AUTHOR]

Peroral administration to mice of melanin isolated from horse chestnut (Aesculus hippocastanum L.) seed shells as an aqueous solution (10%) at doses of 2000, 2500, 3000, 4000, and 5000 mg/kg produced no symptoms of acute toxicity in all experimental animals. The mortality corresponded to class VI relatively harmless compounds (LD50 > 5000 mg/kg). Melanin administered intragastrically at doses of 0.5 and 5.0 mg/kg had an induced effect on humoral immunity. The maximum effectiveness was manifested at a dose of 5.0 mg/kg, where the content of antibody-forming cells in the spleen increased by 4.1 times and was 1.7 times greater than that induced by Immunal. Melanin at the studied doses reliably stimulated the formation of a clone of antigen-specific T-lymphocytes and had a stimulating effect on central and peripheral immunity organs, increasing the number of nucleated cells of the thymus by a maximum of 2.8 times; of the spleen, by 1.7 times; and of the lymph nodes, by 5.7 times, like Immunal. [ABSTRACT FROM AUTHOR]

This study aimed to modify the essential oils of Cymbopogon flexuosus (Nees ex Steud.) W. Watson, hereafter referred to as CF, and Cymbopogon martini (Roxb.) W. Watson, hereafter referred to as CM, utilizing an acid-distillation protocol. The modification resulted in a significant reduction in the aldehyde components, Neral and Geranial, in CF, subsequently leading to the formation of the monoterpene, Cymene. Conversely, the alteration in CM decreased the proportions of the monoterpenol, Geraniol, and the ester, Geranyl acetate. These modifications enhanced the cellular safety of both CF and CM essential oils towards B16-F10 cells in vitro, increasing it by 4 to 8-fold, and concurrently improved their melanin suppression and antioxidant properties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Eumelanin is a natural pigment found in many organisms that provides photoprotection from harmful UV radiation. As a redox‐active biopolymer, the structure of eumelanin is thought to contain different redox states of quinone, including catechol subunits. To further explore the excited state properties of eumelanin, we have investigated the catechol/o‐quinone redox couple by spectroelectrochemical means, in a pH 7.4 aqueous buffered solution, and using a boron doped diamond mesh electrode. At pH 7.4, the two proton, two electron oxidation of catechol is promoted, which facilitates continuous formation of the unstable o‐quinone product in solution. Ultrafast transient absorption (femtosecond to nanosecond) measurements of o‐quinone species involve initial formation of an excited singlet state followed by triplet state formation within 24 ps. In contrast, catechol in aqueous buffer leads to formation of the semiquinone radical Δt>500 ps. Our results demonstrate the rich photochemistry of the catechol/o‐quinone redox couple and provides further insight into the excited state processes of these key building blocks of eumelanin. [ABSTRACT FROM AUTHOR]

This biology lesson uses the science of central dogma to "critique and question the politics of representation that systematically devalue[s] Blackness" (hooks, 131). Students' understanding of protein synthesis is extended in discussing melanin and its significance to protecting the body from harmful radiation from the sun. Through data analysis, students are able to explain the function of melanin and the evolutionary benefits to various skin colors. In addition to a discussion on the biology of skin color and the gene responsible (mc1r), students engage in a lesson that is culturally relevant/responsive. Through challenging racist ideologies and understanding the biology of skin color, students are the center of discussions on racism and the impacts of the social construction of race. The title "Black is Beautiful" is inspired by Jamaican reggae artist Chronixx and the work of Michelle Grace Williams, "They Never Told Us Black is Beautiful: Fostering Black Joy and Pro-Blackness Pedagogies in Early Childhood Classrooms." Through artivism, students challenge eurocentric ideologies on beauty and genius through literary or visual arts. In addition to being an act of activism, artwork will also demonstrate an understanding of melanin's role. [ABSTRACT FROM AUTHOR]

In our previous study, we documented the anti-melanogenic efficacy of calebin-A (CBA), which is a curcuminoid analog. The effects of its newly synthesized analogs, i.e., bisdemethoxy calebin (BD), demethoxycalebin-1 (DA1), demethoxycalebin-2 (DA2), and tetrahydrocalebin-A (THCBA), on melanogenesis have not been examined yet. Herein, we evaluated these four CBA analogs to determine their impacts on the enzymatic activity of mushroom tyrosinase. Additionally, we examined their effects on melanogenesis and the tyrosinase activity in B16F10 mouse and MNT-1 human melanoma cells. The antioxidant activity of the analogs was also assessed. Our results revealed that BD was ineffective, while DA1 and DA2 showed similar antioxidant activities, with THCBA exhibiting the greatest antioxidant activity. Next, the diphenolase activity assay results revealed that DA1 showed the most excellent inhibitory efficacy, DA2 and BD showed similar inhibition profiles, and THCBA was ineffective. In addition, the results of the monophenolase activity showed a similar pattern, except that THCBA suppressed the activity. The four analogs were evaluated for any cytotoxicity over a 48 h duration in B16F10 and HaCaT keratinocytes, where DA1 exerted cytotoxicity at the concentration of 50 µM. Based on this, the analogs were evaluated over a 10–50 µM concentration range, while DA1 was evaluated over 10–35 µM. BD showed the greatest efficacy at multiple concentrations in significantly diminishing melanogenesis in hormone-stimulated B16F10 cells, while DA1 and DA2 suppressed melanin at 35 and 50 µM, respectively, and THCBA stimulated melanogenesis at 50 µM. In addition, BD and DA1 suppressed tyrosinase activity in B16F10 cells, with no effect in the case of DA2 and THCBA analogs. However, in MNT-1 cells, only DA1 showed efficacy in suppressing melanin production while the other three analogs were ineffective. Interestingly, BD and DA1 suppressed MNT-1 cell tyrosinase activity. Collectively, our results indicate that of the four analogs, DA1 merits further investigation as a potential compound for hyperpigmentation skin disorders. Additional research is necessary to delineate the molecular mechanisms underlying the melanogenesis-inhibitory effect of CBA analogs and examine their efficacy in diminishing melanogenesis in normal human melanocytes. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves β-catenin plays a crucial role in promoting the melanin production in melanocytes. Targeted inhibition of the Janus kinase JAK-STAT pathway can effectively diminish the secretion of the chemokine C-X-C motif ligand CXCL10, thereby safeguarding melanocytes. Ferula has been applied as a treatment regimen for a long period; however, its use for the treatment of vitiligo has not been previously documented. Methods: CCK-8 assay, Intracellular melanin content assay, Tyrosinase activity assay, Western blotting, qRT-PCR, and ELISA methods were employed. Using molecular docking verified the inhibitory effects of feshurin on the JAK1. Results: The sesquiterpene coumarin feshurin was separated from Ferula samarcandica. Feshurin was shown to induce GSK-3β phosphorylation, resulting in the translocation of β-catenin into the nucleus. This translocation subsequently upregulated the transcription of microphthalmia-associated transcription factor (MITF), leading to increased tyrosinase activity and melanin production. In addition, feshurin inhibited the production of chemokine CXCL10 via the JAK-STAT signaling pathway, which was verified by molecular docking. Conclusions: Based on these findings, it can be concluded that feshurin exhibits significant potential for the development of novel anti-vitiligo therapeutics. [ABSTRACT FROM AUTHOR]

Fungal contamination poses a serious threat to public health and food safety because molds can grow under stressful conditions through melanin accumulation. Although ultraviolet (UV) irradiation is popular for inhibiting microorganisms, its effectiveness is limited by our insufficient knowledge about UV tolerance in melanin-accumulating molds. In this study, we first confirmed the protective effect of melanin by evaluating the UV sensitivity of young and mature spores. Additionally, we compared UV sensitivity between spores with accumulated melanin and spores prepared with melanin biosynthesis inhibitors. We found that mature spores were less UV-sensitive than young spores, and that reduced melanin accumulation by inhibitors led to reduced UV sensitivity. These results suggest that melanin protects cells against UV irradiation. To determine the most effective wavelength for inhibition, we evaluated the wavelength dependence of UV tolerance in a yeast (Rhodotorula mucilaginosa) and in molds (Aspergillus fumigatus, Cladosporium halotolerans, Cladosporium sphaerospermum, Aspergillus brasiliensis, Penicillium roqueforti, and Botrytis cinerea). We assessed UV tolerance using a UV-light emitting diode (LED) irradiation system with 13 wavelength-ranked LEDs between 250 and 365 nm, a krypton chlorine (KrCl) excimer lamp device, and a low pressure (LP) Hg lamp device. The inhibition of fungi peaked at around 270 nm, and most molds showed reduced UV sensitivity at shorter wavelengths as they accumulated pigment. Absorption spectra of the pigments showed greater absorption at shorter wavelengths, suggesting greater UV protection at these wavelengths. These results will assist in the development of fungal disinfection systems using UV, such as closed systems of air and water purification. [ABSTRACT FROM AUTHOR]

Cladosporium cladosporioides are the pigmented soil fungi containing melanin. The aim of this work was to determine the influence of amphotericin B on free radicals in the natural melanin isolated from pigmented fungi Cladosporium cladosporioides and to compare it with the effect in synthetic DOPA-melanin. Electron paramagnetic resonance (EPR) spectra were measured at X-band (9.3 GHz) with microwave power in the range of 2.2–70 mW. Amplitudes, integral intensities, linewidths of the EPR spectra, and g factors, were analyzed. The concentrations of free radicals in the tested melanin samples were determined. Microwave saturation of EPR lines indicates the presence of pheomelanin in addition to eumelanin in Cladosporium cladosporioides. o-Semiquinone free radicals in concentrations ~1020 [spin/g] exist in the tested melanin samples and in their complexes with amphotericin B. Changes in concentrations of free radicals in the examined synthetic and natural melanin point out their participation in the formation of amphotericin B binding to melanin. A different influence of amphotericin B on free radical concentration in Cladosporium cladosporioides melanin and in DOPA-melanin may be caused by the occurrence of pheomelanin in addition to eumelanin in Cladosporium cladosporioides. The advanced spectral analysis in the wide range of microwave powers made it possible to compare changes in the free radical systems of different melanin polymers. This study is important for knowledge about the role of free radicals in the interactions of melanin with drugs. [ABSTRACT FROM AUTHOR]

This study aimed to examine the structural alterations of the deep gray matter (DGM) in the basal ganglia circuitry of Parkinson's disease (PD) patients with freezing of gait (FOG) using quantitative susceptibility mapping (QSM) and neuromelanin-sensitive magnetic resonance imaging (NM-MRI). Twenty-five (25) PD patients with FOG (PD-FOG), 22 PD patients without FOG (PD-nFOG), and 30 age- and sex-matched healthy controls (HCs) underwent 3-dimensional multi-echo gradient recalled echo and NM-MRI scanning. The mean volume and susceptibility of the DGM on QSM data and the relative contrast (NM RC-SNpc) and volume (NM volume-SNpc) of the substantia nigra pars compacta on NM-MRI were analyzed among groups. A multiple linear regression analysis was performed to explore the associations of FOG severity with MRI measurements and disease stage. The PD-FOG group showed higher susceptibility in the bilateral caudal substantia nigra (SN) compared to the HC group. Both the PD-FOG and PD-nFOG groups showed lower volumes than the HC group in the bilateral caudate and putamen as determined from the QSM data. The NM volume-SNpc on NM-MRI in the PD-FOG group was significantly lower than in the HC and PD-nFOG groups. Both the PD-FOG and PD-nFOG groups showed significantly decreased NM RC-SNpc. The PD-FOG patients showed abnormal neostriatum atrophy, increases in iron deposition in the SN, and lower NM volume-SNpc. The structural alterations of the DGM in the basal ganglia circuits could lead to the abnormal output of the basal ganglia circuit to trigger the FOG in PD patients. [ABSTRACT FROM AUTHOR]

Background: In vitro single‐cell experiments may yield inconsistent results compared to clinical trials. To enhance the reliability of cosmetic active ingredient screening, a coculture model of B16F10‐HaCaT cells was established in vitro based on the structural characteristics of human skin, thereby improving the credibility of experimental outcomes. Currently, most cosmetic whitening additives primarily target simple efficacy goals such as inhibiting tyrosinase activity or melanin transfer. Therefore, investigating novel and efficient whitening additives has become a prominent research focus. Objectives: The aim is to establish an in vitro cell coculture model for more reliable experimental results and investigate the mechanism by which Paeonia lactiflora Pall seeds oil inhibits melanin production and transfer. Methods: The impact of different concentrations of Paeonia lactiflora Pall seeds oil on cocultured cell proliferation rate was assessed using cck8 assay. Tyrosinase inhibition ability in cocultured cells was tested using levodopa as a substrate. Melanin production inhibition ability in coculture cells was evaluated by lysing cells with sodium hydroxide. The effect of Paeonia lactiflora Pall seeds oil on dendrite‐related gene expression levels was examined through qPCR analysis. Additionally, Western blotting was employed to study the effect of Paeonia lactiflora Pall seeds oil on dendrite‐related protein expression levels. Results: Different concentrations of Paeonia lactiflora Pall seeds oil did not affect the proliferation activity of cocultured cells. A specific concentration of α‐MSH increased cell tyrosinase activity, cellular melanin content, as well as Rac1, Cdc42, and PAR‐2 gene and protein expression related to dendritic formation. Treatment with a certain concentration of Paeonia lactiflora Pall seeds oil resulted in decreased tyrosinase activity and melanin content in cells along with downregulated expression levels of Rac1, Cdc42, and PAR‐2 genes and proteins associated with dendritic formation. Conclusions: Paeonia lactiflora Pall seeds oil at specific concentrations exhibits the ability to inhibit tyrosinase activity, decrease melanin content, and possesses the potential to impede melanin transfer. [ABSTRACT FROM AUTHOR]

Excessive ultraviolet (UV) radiation causes a series of adverse effects on human skin, such as erythema and tanning due to the produce of endogenous melanin of human skin. Inspired by the self‐defense mechanism of human skin to prevent UV radiation damage, we construct a natural and biocompatible Carb@PDA−L sunscreen hydrogel by doping melanin‐like L‐lysine doped polydopamine (PDA−L) to biocompatible poly‐γ‐glutamic acid based hydrogel matrix Carb, which displays good biosafety, efficient UV shielding performance and excellent antioxidative and anti‐inflammatory performance in the application of the skin protection of sun and repair after sunburn. The melanin‐like PDA−L can be synthesized by the oxidative polymerization of dopamine triggered by L‐lysine under alkali‐free condition, which exhibits increase absorption intensity in the UV region and better reactive oxygen species removal performance compared with undoped polydopamine in the perspective of a UV absorber. Meanwhile, PDA−L, as the synthetic analogue of natural melanin, has good biosafety, which can avoid the skin oxidative damage and penetrative toxicity of the conventional sunscreen. [ABSTRACT FROM AUTHOR]

Rice is one of the plants proven to possess antioxidant, anti-inflammatory, anti-proliferative, and whitening properties, making it one of the most beneficial plants in this regard. This study aimed to introduce a novel natural cosmetic and pharmaceutical product based on rice callus as a source of active ingredients that can inhibit skin melanoma cell (B16F10) proliferation and brighten the skin. The 2,4-D hormone at concentrations of 1 µg/mL and 1.5 µg/mL was used to induce rice callus formation. Rice callus extracts were then prepared using aqueous and ethanolic solvents, with a concentration of 1 mg/mL used for characterization tests. To determine the optimal hormone concentration, the phenols/flavonoids, antioxidant activity, proteins, and carbohydrates in the extracts were measured. The optimal concentration of the hormone was found to be 1 µg/mL. Finally, the anti-melanocyte and skin-whitening activity of the extracts was assessed through measurements of their cytotoxicity and inhibition of melanin synthesis-related enzymes. Cellular cytotoxicity measurements revealed that the ethanolic extract induced more cytotoxicity than the aqueous extract, with IC50 values of 566.3 µg/mL for the ethanolic extract and 1327 µg/mL for the aqueous extract. Skin-whitening-related tests demonstrated that the extracts were 1.7 times more effective than arbutin in inhibiting factors that cause hyperpigmentation. The aqueous extract achieved 85% inhibition of melanin biosynthesis at a concentration of 3200 µg/mL, compared to 68% for the ethanolic extract and 50% for arbutin. Based on these findings, rice callus extract can be introduced as a new, effective substance for skin-lightening and anti-melanocyte products in cosmeceutical and pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Auricularia auricula melanin has a variety of biological activities, but its application is limited because melanin is not easily soluble in water and most organic solvents. In this study, Auricularia auricula melanin was modified using arginine and analyzed for its structure, physicochemical properties, as well as antioxidant and antibacterial activities. It was found that the water solubility of melanin modified by arginine was 11.6 mg/mL. Arg-melanin is stable under cold dark conditions. Structural analysis by UV, IR and NMR revealed that Auricularia auricula melanin was mainly eumelanin. Arg-melanin exhibited scavenging activities of 75.4%, 76.7%, and 77.6% against DPPH radicals, OH radicals, and O2−, respectively, which were 9.6%, 42.2%, and 31.2% higher than those of melanin. The MICs of melanin and Arg-melanin were 2.5 mg/mL and 1.5 mg/mL against S. aureus, and 3 mg/mL against E. coli. The MIC and MBC values were identical. As the concentration of melanin increased, the strain exhibited greater growth inhibition and more nucleic acid leakage. Arginine modification of melanin can improve its water solubility, and can enhance the antioxidant and bacteriostatic activity of melanin, which provides a theoretical basis for the application of melanin in the field of food and medicine. [ABSTRACT FROM AUTHOR]

Thermal plasticity of melanin pigmentation patterns in Drosophila species has been studied as a model to investigate developmental mechanisms of phenotypic plasticity. The developmental process of melanin pigmentation patterns on wings of Drosophila is divided into two parts, prepattern specification during the pupal period and wing vein-dependent transportation of melanin precursors after eclosion. Which part can be affected by thermal changes? To address this question, we used polka-dotted melanin spots on wings of Drosophila guttifera, whose spot areas are specified by wingless morphogen. In this research, we reared D. guttifera at different temperatures to test whether wing spots show thermal plasticity. We found that wing size becomes larger at lower temperature and that different spots have different reaction norms. Furthermore, we changed the rearing temperature in the middle of the pupal period and found that the most sensitive developmental periods for wing size and spot size are different. The results suggest that the size control mechanisms for the thermal plasticity of wing size and spot size are independent. We also found that the most sensitive stage for spot size was part of the pupal period including stages at which wingless is expressed in the polka-dotted pattern. Therefore, it is suggested that temperature change might affect the prepattern specification process and might not affect transportation through wing veins.