RESUMEN

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 µmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.

Asunto(s)

Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Envejecimiento de la Piel , Rayos Ultravioleta , Envejecimiento de la Piel/efectos de los fármacos , Animales , Humanos , Rayos Ultravioleta/efectos adversos , Ratones , Estrés Oxidativo/efectos de los fármacos , Metaloproteinasas de la Matriz/metabolismo , Queratinocitos/efectos de los fármacos , Ratones Desnudos , Piel/efectos de los fármacos , Piel/patología , Piel/metabolismo , Piel/efectos de la radiación , Células HaCaT , Masculino , Melaninas/metabolismo , Colágeno/metabolismo , Femenino

RESUMEN

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.

Asunto(s)

Pollos , Melaninas , Secuenciación Completa del Genoma , Animales , Pollos/genética , Pollos/metabolismo , Melaninas/metabolismo , Melaninas/genética , Pigmentación de la Piel/genética , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple

RESUMEN

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties.

Asunto(s)

Colágeno , Péptidos , Piel , Animales , Humanos , Piel/efectos de los fármacos , Piel/metabolismo , Colágeno/metabolismo , Péptidos/química , Péptidos/farmacología , Ratones , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Ondas Ultrasónicas , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Células HaCaT , Peso Molecular , Melaninas , Monofenol Monooxigenasa/metabolismo

RESUMEN

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.

Asunto(s)

Anfotericina B , Cladosporium , Melaninas , Melaninas/metabolismo , Cladosporium/efectos de los fármacos , Espectroscopía de Resonancia por Spin del Electrón/métodos , Anfotericina B/farmacología , Radicales Libres/metabolismo , Dihidroxifenilalanina/química , Dihidroxifenilalanina/metabolismo , Dihidroxifenilalanina/análogos & derivados

RESUMEN

Coreopsis tinctoria Nutt. is an important medicinal plant in traditional Uyghur medicine. The skin-lightening potential of the flower has been recognized recently; however, the active compounds responsible for that are not clear. In this work, tyrosinase, a target protein for regulating melanin synthesis, was immobilized on the Whatman paper for the first time to screen skin-lightening compounds present in the flower. Quercetagetin-7-O-glucoside (1), marein (2), and okanin (3) were found to be the enzyme inhibitors. The IC50 values of quercetagetin-7-O-glucoside (1) and okanin (3) were 79.06 ± 1.08 µM and 30.25 ± 1.11 µM, respectively, which is smaller than 100.21 ± 0.11 µM of the positive control kojic acid. Enzyme kinetic analysis and molecular docking were carried out to investigate their inhibition mechanism. Although marein (2) showed a weak inhibition effect in vitro, it inhibited the intracellular tyrosinase activity and diminished melanin production in melanoma B16 cells as did the other two inhibitors. The paper-based ligand fishing method developed in this work makes it effective to quickly screen tyrosinase inhibitors from natural products. This is the first report on the tyrosinase inhibitory effect of those three compounds, showing the promising potential of Coreopsis tinctoria for the development of herbal skin-lightening products.

Asunto(s)

Coreopsis , Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Coreopsis/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Animales , Melaninas/antagonistas & inhibidores , Melaninas/biosíntesis , Ligandos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratones , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/antagonistas & inhibidores , Cinética

RESUMEN

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1-15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 µM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver-Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

Asunto(s)

Melaninas , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Preparaciones para Aclaramiento de la Piel , Pez Cebra , Melaninas/biosíntesis , Melaninas/antagonistas & inhibidores , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Animales , Ratones , Preparaciones para Aclaramiento de la Piel/farmacología , Preparaciones para Aclaramiento de la Piel/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Agaricales/enzimología , Relación Estructura-Actividad , Oxazoles/química , Oxazoles/farmacología , Resorcinoles/química , Resorcinoles/farmacología , Humanos , Estructura Molecular , Pironas

RESUMEN

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.

Asunto(s)

Calcio , Pared Celular , Cryptococcus neoformans , Melaninas , Cryptococcus neoformans/metabolismo , Cryptococcus neoformans/crecimiento & desarrollo , Melaninas/metabolismo , Calcio/metabolismo , Pared Celular/metabolismo , Cápsulas Fúngicas/metabolismo , Humanos , Polisacáridos/metabolismo , Polisacáridos Fúngicos/metabolismo

RESUMEN

OBJECTIVE: Dementia with Lewy bodies (DLB) is recognized as the second most common cause of degenerative dementia in older people with Alzheimer's disease (AD), and distinguishing between these 2 diseases may be challenging in clinical practice. However, accurate differentiation is important because these 2 diseases have different prognoses and require different care. Recently, several studies have reported that neuromelanin-sensitive MRI can detect neurodegeneration in the substantia nigra pars compacta (SNc). DLB patients are considered to demonstrate degeneration and a reduction of dopaminergic neurons in the SNc. Therefore, neuromelanin-sensitive MRI may be useful for the diagnosis of DLB. Therefore, in this study, we aimed to investigate the usefulness of neuromelanin-sensitive MRI in the distinguishing DLB from AD. METHODS: A total of 21 probable DLB and 22 probable AD patients were enrolled. All participants underwent both DaT-SPECT and neuromelanin-sensitive MRI. A combined model of neuromelanin-sensitive MRI and Dopamine transporter single-photon emission computed tomography (DaT-SPECT) was created using logistic regression analysis (forced entry method). RESULTS: There was no difference in the diagnostic utility of neuromelanin-sensitive MRI and DaT-SPECT in distinguishing DLB from AD. There was no significant correlation between the results of neuromelanin-sensitive MRI and DaT-SPECT in DLB patients. The combination of neuromelanin-sensitive MRI and DaT-SPECT demonstrated higher diagnostic performance in distinguishing between DLB and AD compared with neuromelanin-sensitive MRI alone. Additionally, although the combination of both modalities showed a larger AUC compared with DaT-SPECT alone, the difference was not statistically significant. CONCLUSIONS: Neuromelanin-sensitive MRI may be equally or even more useful than DaT-SPECT in the clinical differentiation of DLB from AD. Furthermore, the combination of neuromelanin-sensitive MRI and DaT-SPECT may be a highly sensitive imaging marker for distinguishing DLB from AD.

Asunto(s)

Enfermedad por Cuerpos de Lewy , Imagen por Resonancia Magnética , Melaninas , Tomografía Computarizada de Emisión de Fotón Único , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/metabolismo , Enfermedad por Cuerpos de Lewy/diagnóstico , Melaninas/metabolismo , Femenino , Anciano , Masculino , Imagen por Resonancia Magnética/métodos , Anciano de 80 o más Años , Tomografía Computarizada de Emisión de Fotón Único/métodos , Diagnóstico Diferencial , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo

RESUMEN

Significance: Hyperspectral cameras capture spectral information at each pixel in an image. Acquired spectra can be analyzed to estimate quantities of absorbing and scattering components, but the use of traditional fitting algorithms over megapixel images can be computationally intensive. Deep learning algorithms can be trained to rapidly analyze spectral data and can potentially process hyperspectral camera data in real time. Aim: A hyperspectral camera was used to capture 1216 × 1936 pixel wide-field reflectance images of in vivo human tissue at 205 wavelength bands from 420 to 830 nm. Approach: The optical properties of oxyhemoglobin, deoxyhemoglobin, melanin, and scattering were used with multi-layer Monte Carlo models to generate simulated diffuse reflectance spectra for 24,000 random combinations of physiologically relevant tissue components. These spectra were then used to train an artificial neural network (ANN) to predict tissue component concentrations from an input reflectance spectrum. Results: The ANN achieved low root mean square errors in a test set of 6000 independent simulated diffuse reflectance spectra while calculating concentration values more than 4000× faster than a conventional iterative least squares approach. Conclusions: In vivo finger occlusion and gingival abrasion studies demonstrate the ability of this approach to rapidly generate high-resolution images of tissue component concentrations from a hyperspectral dataset acquired from human subjects.

Asunto(s)

Aprendizaje Profundo , Hemoglobinas , Imágenes Hiperespectrales , Melaninas , Humanos , Melaninas/análisis , Melaninas/química , Hemoglobinas/análisis , Imágenes Hiperespectrales/métodos , Método de Montecarlo , Dispersión de Radiación , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Redes Neurales de la Computación , Dedos/diagnóstico por imagen

RESUMEN

Lichens are important components of high-latitude boreal and Arctic habitats. While stress tolerant, they are among the most sensitive ecosystem components to climate change, in particular, an increase in ultraviolet light (UV) arising from polar ozone depletion and deforestation. This study is the first to explore the effects of UV-B on gene expression in lichens to predict metabolic pathways involved in tolerance. Using transcriptome profiling and bioinformatic analyses, here we studied the effects of UV-B on gene expression in lichens using Lobaria pulmonaria (L.) Hoff. as a model species. UV-B exposure causes significant browning of the upper cortex of the thallus, which correlates to an increased expression of biosynthetic gene clusters involved in the synthesis of eu- and allomelanins and melanin precursors. Based on transcriptome analyses, we suggest that the biosynthesis of melanins and other secondary metabolites, such as naphthalene derivates, tropolones, anthraquinones, and xanthones, is a trade-off that lichens pay to protect essential metabolic processes such as photosynthesis and respiration. Expression profiles of general stress-associated genes, in particular, related to reactive oxygen species scavenging, protection of proteins, and DNA repair, clearly indicate that the mycobiont is the more UV-B-responsive and susceptible partner in lichen symbiosis. Our findings demonstrate that UV-B stress activates an intricate gene network involved in tolerance mechanisms of lichen symbionts. Knowledge obtained here may enable the prediction of likely effects on lichen biodiversity caused by climate change and pollution.

Asunto(s)

Líquenes , Transcriptoma , Rayos Ultravioleta , Líquenes/fisiología , Líquenes/efectos de la radiación , Líquenes/genética , Líquenes/metabolismo , Melaninas/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de la radiación

RESUMEN

Melanin naturally exists in organisms and is synthetized by tyrosinase (TYR); however, its over-production may lead to aberrant pigmentation and skin conditions. Loquat (Eriobotrya japonica (Thunb.) Lindl.) flowers contain a variety of bioactive compounds, while studies on their suppressive capabilities against melanin synthesis are limited. Loquat flower isolate product (LFP) was obtained by ethanol extraction and resin purification, and its inhibitory efficiency against TYR activity was investigated by enzyme kinetics and multiple spectroscopy analyses. In addition, the impact of LFP on melanin synthesis-related proteins' expression in mouse melanoma B16 cells was analyzed using Western blotting. HPLC-MS/MS analysis indicated that LFP was composed of 137 compounds, of which 12 compounds, including flavonoids (quercetin, isorhamnoin, p-coumaric acid, etc.) and cinnamic acid and its derivatives, as well as benzene and its derivatives, might have TYR inhibitory activities. LFP inhibited TYR activity in a concentration-dependent manner with its IC50 value being 2.8 mg/mL. The inhibition was an anti-competitive one through altering the enzyme's conformation rather than chelating copper ions at the active center. LFP reduced the expression of TYR, tyrosinase-related protein (TRP) 1, and TRP2 in melanoma B16 cells, hence inhibiting the synthesis of melanin. The research suggested that LFP had the potential to reduce the risks of hyperpigmentation caused by tyrosinase and provided a foundation for the utilization of loquat flower as a natural resource in the development of beauty and aging-related functional products.

Asunto(s)

Eriobotrya , Flores , Melaninas , Melanoma Experimental , Monofenol Monooxigenasa , Extractos Vegetales , Animales , Monofenol Monooxigenasa/metabolismo , Monofenol Monooxigenasa/antagonistas & inhibidores , Ratones , Melaninas/biosíntesis , Melaninas/metabolismo , Flores/química , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Eriobotrya/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Línea Celular Tumoral , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química

RESUMEN

The Bletilla striata polysaccharides (BSP) extracted through alkali-assisted method exhibit significant antioxidant activity, but its bioaccessibility was inadequate due to its tightly filamentous reticulation structure and high molecular weight. The anti-photoaging and anti-melanogenesis effects of degraded BSP (DBSPs) against UVB-induced oxidative stress on the skin were investigated. The molecular weights of the DBSPs were reduced to 153.94 kDa, 66.96 kDa, and 15.54 kDa from an initial value of 298.82 kDa. The degradation treatment altered the branched chain structure of the DBSPs, while the backbone structure, triple-helix structure, and crystallinity remained. DBSPs with a lower molecular weight exhibit better in vitro antioxidant activity. DBSPs did not show cytotoxicity to HSF cells but inhibited B16F10 cell proliferation. The addition of DBSPs protected HSF and B16F10 cells from oxidative stress and reduced ROS levels, B16F10 melanin content, and B16F10 tyrosinase activity after UVB damage, but DBSP-10 particles were slightly less effective due to aggregation. In contrast, DBSP-5 demonstrated effectiveness in reducing MDA levels in cells stressed by oxidative stress, increased total antioxidant capacity, and inhibited melanogenesis in B16F10, suggesting that DBSP-5 has potential as a topical therapeutic agent for the treatment of skin diseases associated with oxidative stress.

Asunto(s)

Antioxidantes , Estrés Oxidativo , Polisacáridos , Piel , Rayos Ultravioleta , Estrés Oxidativo/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Polisacáridos/farmacología , Polisacáridos/química , Animales , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Ratones , Antioxidantes/farmacología , Antioxidantes/química , Orchidaceae/química , Melaninas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Humanos , Peso Molecular , Proliferación Celular/efectos de los fármacos

RESUMEN

Bacterial infection is one of the most problematic issues for human health and the resistance of bacteria to traditional antibiotics is a matter of huge concern. Therefore, research is focusing on the development of new strategies to efficiently kill these microorganisms. Recently, melanin is starting to be investigated for this purpose. Indeed, this very versatile material presents outstanding photothermal properties, already studied for photothermal therapy, which can be very useful for the light-induced eradication of bacteria. In this review, we present antibacterial melanin applications based on the photothermal effect, focusing both on the single action of melanin and on its combination with other antibacterial systems. Melanin, also thanks to its biocompatibility and ease of functionalization, has been demonstrated to be easily applicable as an antimicrobial agent, especially for the treatment of local infections.

Asunto(s)

Antibacterianos , Melaninas , Melaninas/química , Melaninas/metabolismo , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Terapia Fototérmica/métodos , Animales , Antiinfecciosos/farmacología , Antiinfecciosos/química , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/terapia

RESUMEN

Lichens have developed numerous adaptations to optimize their survival in various environmental conditions, largely by producing secondary compounds by the fungal partner. They often have antibiotic properties and are involved in protection against intensive UV radiation, pathogens, and herbivores. To contribute to the knowledge of the arsenal of secondary compounds in a crustose lichen species, we sequenced and assembled the genome of Toniniopsis dissimilis, an indicator of old-growth forests, using Oxford Nanopore Technologies (ONT, Oxford, UK) long reads. Our analyses focused on biosynthetic gene clusters (BGCs) and specifically on Type I Polyketide (T1PKS) genes involved in the biosynthesis of polyketides. We used the comparative genomic approach to compare the genome of T. dissimilis with six other members of the family Ramalinaceae and twenty additional lichen genomes from the database. With only six T1PKS genes, a comparatively low number of biosynthetic genes are present in the T. dissimilis genome; from those, two-thirds are putatively involved in melanin biosynthesis. The comparative analyses showed at least three potential pathways of melanin biosynthesis in T. dissimilis, namely via the formation of 1,3,6,8-tetrahydroxynaphthalene, naphthopyrone, or YWA1 putative precursors, which highlights its importance in T. dissimilis. In addition, we report the occurrence of genes encoding ribosomally synthesized and posttranslationally modified peptides (RiPPs) in lichens, with their highest number in T. dissimilis compared to other Ramalinaceae genomes. So far, no function has been assigned to RiPP-like proteins in lichens, which leaves potential for future research on this topic.

Asunto(s)

Genoma Fúngico , Líquenes , Melaninas , Melaninas/biosíntesis , Melaninas/genética , Líquenes/genética , Líquenes/metabolismo , Familia de Multigenes , Filogenia , Vías Biosintéticas/genética , Ascomicetos/genética , Ascomicetos/metabolismo , Policétidos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo

RESUMEN

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

Asunto(s)

Inhibidores Enzimáticos , Melaninas , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Péptidos , Pinctada , Animales , Monofenol Monooxigenasa/antagonistas & inhibidores , Péptidos/farmacología , Péptidos/química , Péptidos/aislamiento & purificación , Ratones , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Melaninas/antagonistas & inhibidores , Línea Celular Tumoral , Melanoma Experimental/tratamiento farmacológico , Simulación de Dinámica Molecular , Simulación por Computador , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación

RESUMEN

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.

Asunto(s)

Melaninas , Rayos Ultravioleta , Melaninas/química , Melaninas/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Fluorescencia , Humanos

RESUMEN

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

Asunto(s)

Hierro , Melaninas , Neuronas , Enfermedad de Parkinson , Sustancia Negra , Sincrotrones , Sustancia Negra/metabolismo , Sustancia Negra/patología , Humanos , Hierro/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Melaninas/metabolismo , Neuronas/metabolismo , Neuronas/patología , Núcleo Celular/metabolismo

RESUMEN

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

Asunto(s)

Antioxidantes , Melaninas , Monofenol Monooxigenasa , Preparaciones para Aclaramiento de la Piel , Animales , Humanos , Ratones , alfa-MSH/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Peces , Células HaCaT , Peróxido de Hidrógeno/farmacología , Melaninas/biosíntesis , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Factor de Transcripción Asociado a Microftalmía/metabolismo , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Oligopéptidos/farmacología , Oligopéptidos/química , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Receptor de Melanocortina Tipo 1/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Preparaciones para Aclaramiento de la Piel/farmacología , Pigmentación de la Piel/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Autofagia , Ceramidas , Melaninas , Melanoma Experimental , Melanosomas , MicroARNs , Transducción de Señal , Serina-Treonina Quinasas TOR , MicroARNs/genética , MicroARNs/metabolismo , Animales , Ratones , Serina-Treonina Quinasas TOR/metabolismo , Melanosomas/metabolismo , Ceramidas/metabolismo , Melaninas/metabolismo , Melaninas/biosíntesis , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Melanoma Experimental/genética , Línea Celular Tumoral , alfa-MSH/metabolismo , Melanocitos/metabolismo , Melanocitos/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Ácidos Borónicos , Indoles , Melaninas , Polímeros , Polímeros/química , Melaninas/química , Melaninas/metabolismo , Indoles/química , Ácidos Borónicos/química , Microalgas/metabolismo , Microalgas/química