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.

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.

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.

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.

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.

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.

Establishment of a promising vitiligo mouse model for pathogenesis and treatment studies.

AIMS: Vitiligo is a chronic dermatological condition characterized by the progressive loss of melanocytes, for which traditional therapy has shown limited efficacy. This study aimed to establish a vitiligo model with easy operability, high repeatability, and stable depigmentation to provide a foundation for studying the pathogenesis and developing novel therapies for vitiligo. METHODS: (1) Establishing vitiligo model: Firstly, deliver B16F10 cells to the back skin of C57BL/6 J via intradermal injection (day 0), and the CD4 depletion antibody was injected intraperitoneally on day 4 and 10. Secondly, the melanoma was surgically removed on day 12. Thirdly, CD8 antibody was administered intraperitoneally every fourth day till day 30. (2) Identification of vitiligo model: H&E staining, immunohistochemistry, and immunofluorescence were used to detect the melanocytes. The melanin was detected by transmission electron microscopy (TEM), Lillie ferrous sulfate staining and L-DOPA staining. RESULTS: (1) The back skin and hair began to appear white on day 30. Melanin loss reached peak on day 60; (2) Hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence results showed melanocytes were reduced. L-DOPA staining, Lillie ferrous sulfate staining and TEM results showed that melanin decreased in the epidermis. CONCLUSION: We successfully establishment a vitiligo mouse model which can be more capable to simulate the pathogenesis of human vitiligo and provide an important basis for the study of pathogenesis and therapy of vitiligo.

MORPHOLOGICAL AND BEHAVIORAL ANALYSIS OF THE PROTECTIVE EFFECTS OF BACTERIAL MELANIN IN A RAT MODEL OF PARKINSON'S DISEASE.

A comparative study of the morphological and functional state of the microvasculature of the substantia nigra pars compacta of the brain (SNc) and bone marrow of rats was carried out using the rotenone model of Parkinson's disease (PD) and with subsequent administration of bacterial melanin (BM). The detection of microvasculature was carried out according to the histoangiological method of Chilingaryan. Animal behavior was studied using a cylinder test. An analysis of morphometric data showed that, in comparison with control animals, experimental animals with rotenone dysfunction showed an increase in capillary diameters and a general reduction in the capillary link in SNc. Behavioral tests have shown that the animals with rotenone intoxication exhibit a form of behavior inherent in PD (freezing, immobility, apathy). Under the influence of BM, the diameter of the capillaries in the SNc approaches the norm, and the capillary link is restored. Due to the protective effect of BM in rats with rotenone intoxication, the trophism of the brain tissue increases as a result of the approach of the lumen of the vessels to the norm and the opening of new branches in the capillary network, an increase in the density of capillaries, which ensures the safety of nerve cells. Animal behavior indicators are close to normal. A comprehensive analysis of cytogenetic data of rat bone marrow was also carried out. In animals with PD, compared to controls, there is a significant increase in the amount of polyploid cells (PC) and a decrease in the level of mitotic index (MI), which usually manifests itself in inflammatory processes and is accompanied by inhibition of bone marrow hematopoiesis. Under the influence of BM, a tendency towards normalization of MI was noted and a significant decrease in the percentage of PC was obtained, which possibly indicates its beneficial effect. The data obtained suggest that BM can be used as a therapeutic agent in the treatment of PD.

Electrospun fibrillary scaffold for electrochemical cell biomarkers detection.

A novel scaffold for in situ electrochemical detection of cell biomarkers was developed using electrospun nanofibers and commercial adhesive polymeric membranes. The electrochemical sensing of cell biomarkers requires the cultivation of the cells on/near the (bio)sensor surface in a manner to preserve an appropriate electroactive available surface and to avoid the surface passivation and sensor damage. This can be achieved by employing biocompatible nanofiber meshes that allow the cells to have a normal behavior and do not alter the electrochemical detection. For a better mechanical stability and ease of handling, nylon 6/6 nanofibers were collected on commercial polymeric membranes, at an optimal fiber density, obtaining a double-layered platform. To demonstrate the functionality of the fabricated scaffold, the screening of cellular stress has been achieved integrating melanoma B16-F10 cells and the (bio)sensor components on the transducer whereas the melanin exocytosis was successfully quantified using a commercial electrode. Either directly on the surface of the (bio)sensor or spatially detached from it, the integration of cell cultures in biosensing platforms based on electrospun nanofibers represents a powerful bioanalytical tool able to provide real-time information about the biomarker release, enzyme activity or inhibition, and monitoring of various cellular events.

Pathogenic strategies of Pseudogymnoascus destructans during torpor and arousal of hibernating bats.

Millions of hibernating bats across North America have died from white-nose syndrome (WNS), an emerging disease caused by a psychrophilic (cold-loving) fungus, Pseudogymnoascus destructans, that invades their skin. Mechanisms of P. destructans invasion of bat epidermis remain obscure. Guided by our in vivo observations, we modeled hibernation with a newly generated little brown bat (Myotis lucifugus) keratinocyte cell line. We uncovered the stealth intracellular lifestyle of P. destructans, which inhibits apoptosis of keratinocytes and spreads through the cells by two epidermal growth factor receptor (EGFR)-dependent mechanisms: active penetration during torpor and induced endocytosis during arousal. Melanin of endocytosed P. destructans blocks endolysosomal maturation, facilitating P. destructans survival and germination after return to torpor. Blockade of EGFR aborts P. destructans entry into keratinocytes.

Growth on Douglas fir media facilitates Cryptococcus virulence factor production and enhances fungal survival against environmental and immune stressors.

The yeasts Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that can be isolated from the environment, including the surfaces of many plants. Cryptococcus gattii caused an outbreak on Vancouver Island, British Columbia beginning in 1999 that has since spread to the Pacific Northwest of the United States. Coastal Douglas fir (Pseudotsuga menziesii) is an important lumber species and a major component of the ecosystems in this area. Previous research has explored Cryptococcus survival and mating on Douglas fir plants and plant-derived material, but no studies have been done on the production of cryptococcal virulence factors by cells grown on those media. Here, we investigated the effects of growth on Douglas fir-derived media on the production of the polysaccharide capsule and melanin, two of the most important cryptococcal virulence factors. We found that while the capsule was mostly unchanged by growth in Douglas fir media compared to cells grown in defined minimal media, Cryptococcus spp. can use substrates present in Douglas fir to synthesize functional and protective melanin. These results suggest mechanisms by which Cryptococcus species may survive in the environment and emphasize the need to explore how association with Douglas fir trees could affect its epidemiology for human cryptococcosis.

Cryptococcus gattii is a fungal pathogen that can be found in the environment. It is responsible for causing an outbreak in British Columbia, Canada, in the late 90s. In our study, we created media from Douglas fir, a tree commonly found in the affected areas. We examined the production of virulence factors by Cryptococcus cells grown in this media.

Fungal melanin suppresses airway epithelial chemokine secretion through blockade of calcium fluxing.

Respiratory infections caused by the human fungal pathogen Aspergillus fumigatus are a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been fully defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of the chemokines CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction in neutrophil recruitment to the apical airway both in vitro and in vivo. Aspergillus-derived melanin, a major constituent of the fungal cell wall, dampened airway epithelial chemokine secretion in response to fungi, bacteria, and exogenous cytokines. Furthermore, melanin muted pathogen-mediated calcium fluxing and hindered actin filamentation. Taken together, our results reveal a critical role for melanin interaction with airway epithelium in shaping the host response to fungal and bacterial pathogens.

Melanin accumulation in acanthotic seborrheic keratosis: Reduced proliferation and early differentiation of keratinocytes and increased number of melanocytes.

Seborrheic keratosis (SK) is a common benign tumour, often associated with hyperpigmentation. To investigate the mechanism of melanin accumulation in SK, we have conducted comprehensive gene expression and histological analyses. We obtained five pairs of skin samples, including non-lesional and SK samples, from the backs of three male Japanese participants aged 40-59 years. To examine melanocytes and keratinocytes in SK, three pairs of skin samples were separated by laser capture microdissection into the basal layer and the other layer in the epidermis. We performed a comprehensive gene expression analysis to identify differentially expressed genes between non-lesional and SK skin, followed by gene ontology and pathway analysis. We found abnormal morphogenesis and cell proliferation in the basal layer, along with increased immune response and impaired cell differentiation and metabolism in the other layer of SK. We focused on cell proliferation and differentiation, as these are directly associated with melanin accumulation. Immunohistochemical analyses of Ki67, keratin 10, and keratin 14 demonstrated the decreases in the proliferation and early differentiation of the epidermis. Contrarily, no significant changes were observed in terminal differentiation markers, filaggrin and loricrin. Although the number of melanocytes was higher in SK than in non-lesional skin, melanogenic activity showed no difference. These results indicated that melanin accumulation in SK is caused by delayed melanin excretion due to reduced turnover around the basal and spinous layers of the epidermis and melanin production due to an increased number of melanocytes. Our findings provide new insights for therapeutic approaches in SK.

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.

Redox pathways in melanoma.

Cases of melanoma are doubling every 12 years, and in stages III and IV, the disease is associated with high mortality rates concomitant with unresectable metastases and therapeutic drug resistance. Despite some advances in treatment success, there is a marked need to understand more about the pathology of the disease. The present review provides an overview of how melanoma cells use and modulate redox pathways to facilitate thiol homeostasis and melanin biosynthesis and describes plausible redox targets that may improve therapeutic approaches in managing malignant disease and metastasis. Melanotic melanoma has some unique characteristics. Making melanin requires a considerable dedication of cellular energy resources and utilizes glutathione and glutathione transferases in certain steps in the biosynthetic pathway. Melanin is an antioxidant but is also functionally important in hematopoiesis and influential in various aspects of host immune responses, giving it unique characteristics. Together with other redox traits that are specific to melanoma, a discussion of possible therapeutic approaches is also provided.

Amorosia littoralis Mantle & D. Hawksw. survives as root endophyte of mangroves and produces water soluble melanin pigment.

Melanins are heterogenous biopolymers produced by many macro and microorganisms. They enhance the ecological fitness of the producer organisms by improving their virulence and protecting them from radiation, osmotic and heat stresses. Fungi synthesise either DOPA or DHN melanin and deposit them on their cell walls. Some fungal isolates produce water soluble melanin (pyomelanin) which is excerted out of the hyphae into the surrounding environment. Pyomelanin, a polymer of homogentisate, exhibits antimicrobial, UV screening, antioxidative, and anti-inflammatory activities and recent studies also show that pyomelanin could find use in space travel as radiation shield. However, scant literature is available on fungi with ability to produce pyomelanin. We report for the first time that Amorosia littoralis occurs as a root endophyte in mangrove species including Avicennia marina, Bruguiera cylindrica and Bruguiera gymnorhiza and produces pyomelanin. Considering the various technological uses of pyomelanin, this study underscores the need to explore fungi of different habitats to identify hyperproducers and to obtain chemically diverse pyomelanin.