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Cells May 2023Based on traditional pharmacological applications and partial in vitro data, (CA) is proposed to act on skin whitening. However, its functional evaluation and...
Based on traditional pharmacological applications and partial in vitro data, (CA) is proposed to act on skin whitening. However, its functional evaluation and underlying mechanisms have yet to be identified. This study aimed to examine the anti-melanogenesis activity of CA fraction B (CAFB) on UVB-induced skin hyperpigmentation. Forty C57BL/6j mice were exposed to UVB (100 mJ/cm, five times/week) for eight weeks. After irradiation, CAFB was applied to the left ear once a day for 8 weeks (the right ear served as an internal control). The results showed that CAFB significantly reduced melanin production in the ear skin, as indicated by the gray value and Mexameter melanin index. In addition, CAFB treatment notably decreased melanin production in α-MSH-stimulated B16F10 melanocytes, along with a significant reduction in tyrosinase activity. Cellular cAMP (cyclic adenosine monophosphate), MITF (microphthalmia-associated transcription factor), and tyrosinase-related protein 1 (TRP1) were also noticeably downregulated by CAFB. In conclusion, CAFB is a promising ingredient for treating skin disorders caused by the overproduction of melanin and its underlying mechanisms involving the modulation of tyrosinase, mainly mediated by the regulation of the cAMP cascade and MITF pathway.
Topics: Animals; Mice; Melanins; Vincetoxicum; Monophenol Monooxygenase; Microphthalmia-Associated Transcription Factor; Signal Transduction; Mice, Inbred C57BL
PubMed: 37408224
DOI: 10.3390/cells12101390 -
Genes Nov 2022Tengchong snow, which has white feathers and black meat, is one of the most important black-bone chicken breeds and a genetic treasure of black food in China. Although...
Tengchong snow, which has white feathers and black meat, is one of the most important black-bone chicken breeds and a genetic treasure of black food in China. Although the black meat traits are dominant, there are some chickens with white meat traits born in the process of folk selection and breeding. The purpose of this study was to compare the differences in skeletal muscle development between Tengchong snow black meat chickens (BS) and white meat chickens (WS), as well as whether excessive melanin deposition has an effect on skeletal muscle development. The BS and WS groups were selected to determine their muscle development difference at stages of 1, 7, 14, 21, and 42 days, using histological stain methods to analyze the development and composing type of breast and leg muscle fibers, as well as the count of melanin in BS muscle fibers. Finally, we were validated key candidate genes associated with muscle development and melanin synthesis. The results showed that BS breast muscle development was inhibited at 7, 14, and 21 days, while the leg muscle was inhibited at 7, 14, 21, and 42 days, compared to WS. Melanin deposition was present in a temporal migration pattern and was greater in the leg muscles than in the breast muscles, and it focused around blood vessels, as well as the epithelium, perimysium, endomysium, and connective tissue. Additionally, melanin produced an inhibitory effect similar to MSTN during skeletal muscle fiber development, and the inhibition was strongest at the stage of melanin entry between muscle fibers, but the precise mechanisms need to be confirmed. This study revealed that melanin has an inhibitory effect on the early development of skeletal muscle, which will provide new insights into the role of melanin in the black-boned chicken and theoretical references for the future conservation and utilization of black-boned chicken.
Topics: Animals; Chickens; Melanins; Snow; Muscle, Skeletal; Hyperpigmentation; Muscle Development
PubMed: 36553521
DOI: 10.3390/genes13122253 -
Proceedings of the National Academy of... Aug 2023Hypothalamic inflammation reduces appetite and body weight during inflammatory diseases, while promoting weight gain when induced by high-fat diet (HFD). How...
Hypothalamic inflammation reduces appetite and body weight during inflammatory diseases, while promoting weight gain when induced by high-fat diet (HFD). How hypothalamic inflammation can induce opposite energy balance outcomes remains unclear. We found that prostaglandin E (PGE), a key hypothalamic inflammatory mediator of sickness, also mediates diet-induced obesity (DIO) by activating appetite-promoting melanin-concentrating hormone (MCH) neurons in the hypothalamus in rats and mice. The effect of PGE on MCH neurons is excitatory at low concentrations while inhibitory at high concentrations, indicating that these neurons can bidirectionally respond to varying levels of inflammation. During prolonged HFD, endogenous PGE depolarizes MCH neurons through an EP2 receptor-mediated inhibition of the electrogenic Na/K-ATPase. Disrupting this mechanism by genetic deletion of EP2 receptors on MCH neurons is protective against DIO and liver steatosis in male and female mice. Thus, an inflammatory mediator can directly stimulate appetite-promoting neurons to exacerbate DIO and fatty liver.
Topics: Mice; Rats; Male; Female; Animals; Obesity; Melanins; Hypothalamus; Inflammation; Fatty Liver; Diet, High-Fat; Neurons; Inflammation Mediators; Prostaglandins
PubMed: 37467285
DOI: 10.1073/pnas.2302809120 -
The Yale Journal of Biology and Medicine Mar 2020The relationship between skin color and skin cancer is well established: the less melanin in one's skin the greater the risk for developing skin cancer. This review is... (Review)
Review
The relationship between skin color and skin cancer is well established: the less melanin in one's skin the greater the risk for developing skin cancer. This review is in two parts. First, we summarize the current understanding of the cutaneous pigmentary system and trace melanin from its synthesis in the pigment cell melanosomes through its transfer to keratinocytes. We also present new methods for reducing melanin content in hyper-pigmented areas of skin such as solar lentigenes, melasma, and post-inflammatory hyperpigmentation. Second, we present evidence that at least one mechanism for the development of metastatic melanoma and other solid tumors is fusion and hybridization of leucocytes such as macrophages with primary tumor cells. In this scenario, hybrid cells express both the chemotactic motility of the leucocyte and the de-regulated cell division of the tumor cell, causing the cells to migrate a deadly journey to lymph nodes, distant organs, and tissues.
Topics: Humans; Hyperpigmentation; Melanins; Skin Neoplasms; Skin Pigmentation
PubMed: 32226338
DOI: No ID Found -
MBio Jun 2023Aspergillus fumigatus is an environmental fungus that can cause life-threatening pulmonary disease. Infections initiate when conidia are inhaled and land deep inside the...
Aspergillus fumigatus is an environmental fungus that can cause life-threatening pulmonary disease. Infections initiate when conidia are inhaled and land deep inside the small airways and alveoli of the lungs, where they interact with epithelial cells. These cells provide a physical barrier and secrete chemokines to attract innate immune cells to the site of infection. Melanin, a key constituent of the conidial cell wall, is required for the establishment of invasive infection due to its ability to inhibit the function of innate immune cells recruited to clear the infection. Here, we provide evidence for an additional mechanism by which A. fumigatus can alter host innate immune responses. infection of a normal human small airway epithelial cell line (HSAEC1-KT) caused a decrease in extracellular protein levels of CXCL10 and CCL20, two proinflammatory chemokines that are required for the host defense against aspergillosis, despite a dramatic increase in the levels of each mRNA. A. fumigatus depleted recombinant human CXCL10 and CCL20 from medium in the absence of host cells, suggesting that the block in accumulation is downstream of protein translation and secretion. Melanin is both necessary and sufficient for this chemokine-depleting activity because a dihydroxynaphthalene (DHN)-melanin-deficient strain of A. fumigatus is defective in depleting chemokines and purified melanin ghosts retain potent depletion activity. We propose that A. fumigatus, through the action of melanin, depletes important chemokines, thereby dampening the innate immune response to promote infection. Aspergillus fumigatus is the major airborne fungal pathogen that affects humans. In order to cause an invasive infection, inhaled spores must avoid killing by innate immune cells that are recruited to the site of infection. Understanding how A. fumigatus achieves immune evasion is important for the development of novel therapeutics. We provide evidence that melanin, a pigment contained in the spore cell wall, can remove certain chemokines from the extracellular space to suppress the host inflammatory response that is responsible for clearing fungal infection.
Topics: Humans; Melanins; Aspergillus fumigatus; Aspergillosis; Chemokines; Spores, Fungal
PubMed: 37067432
DOI: 10.1128/mbio.00194-23 -
Scientific Reports May 2022Lower vertebrates, including fish, can rapidly alter skin lightness through changes in melanin concentration and melanosomes' mobility according to various factors,...
Lower vertebrates, including fish, can rapidly alter skin lightness through changes in melanin concentration and melanosomes' mobility according to various factors, which include background color, light intensity, ambient temperature, social context, husbandry practices and acute or chronic stressful stimuli. Within this framework, the determination of skin chromaticity parameters in fish species is estimated either in specific areas using colorimeters or at the whole animal level using image processing and analysis software. Nevertheless, the accurate quantification of melanin content or melanophore coverage in fish skin is quite challenging as a result of the laborious chemical analysis and the typical application of simple optical imaging methods, requiring also to euthanize the fish in order to obtain large skin samples for relevant investigations. Here we present the application of a novel hybrid confocal fluorescence and photoacoustic microscopy prototype for the label-free imaging and quantification of melanin in fish scales samples with high spatial resolution, sensitivity and detection specificity. The hybrid images are automatically processed through optimized algorithms, aiming at the accurate and rapid extraction of various melanin accumulation indices in large datasets (i.e., total melanin content, melanophores' area, density and coverage) corresponding to different fish species and groups. Furthermore, convolutional neural network-based algorithms have been trained using the recorded data towards the classification of different scales' samples with high accuracy. In this context, we demonstrate that the proposed methodology may increase substantially the precision, as well as, simplify and expedite the relevant procedures for the quantification of melanin content in marine organisms.
Topics: Animals; Melanins; Melanophores; Microscopy; Skin Pigmentation; Spectrum Analysis
PubMed: 35504968
DOI: 10.1038/s41598-022-11262-0 -
Communications Biology Dec 2022A key component of the insect immune response is melanin production, including within nodules, or aggregations of immune cells surrounding microbes. Melanization...
A key component of the insect immune response is melanin production, including within nodules, or aggregations of immune cells surrounding microbes. Melanization produces oxidative and toxic intermediates that limit microbial infections. However, a direct fungicidal role of melanin during infection has not been demonstrated. We previously reported that the fungus Cryptococcus neoformans is encapsulated with melanin within nodules of Galleria mellonella hosts. Here we developed techniques to study melanin's role during C. neoformans infection in G. mellonella. We provided evidence that in vivo melanin-encapsulation was fungicidal. To further study immune melanization, we applied tissue-clearing techniques to visualize melanized nodules in situ throughout the larvae. Further, we developed a time-lapse microscopy protocol to visualize the melanization kinetics in extracted hemolymph following fungal exposure. Using this technique, we found that cryptococcal melanin and laccase enhance immune melanization. We extended this approach to study the fungal pathogens Candida albicans and Candida auris. We find that the yeast morphologies of these fungi elicited robust melanization responses, while hyphal and pseudohyphal morphologies were melanin-evasive. Approximately 23% of melanin-encapsulated C. albicans yeast can survive and breakthrough the encapsulation. Overall, our results provide direct evidence that immune melanization functions as a direct antifungal mechanism in G. mellonella.
Topics: Animals; Moths; Cryptococcus neoformans; Cryptococcosis; Candida albicans; Hemolymph; Melanins; Fungicides, Industrial
PubMed: 36510005
DOI: 10.1038/s42003-022-04340-6 -
Journal of Controlled Release :... Aug 2022Melanin binding of drugs is known to increase drug concentrations and retention in pigmented eye tissues. Even though the correlation between melanin binding in vitro...
Melanin binding of drugs is known to increase drug concentrations and retention in pigmented eye tissues. Even though the correlation between melanin binding in vitro and exposure to pigmented eye in vivo has been shown, there is a discrepancy between rapid drug release from melanin particles in vitro and the long in vivo retention in the pigmented tissues. We investigated mechanisms and kinetics of pigment-related drug retention experimentally using isolated melanin particles from porcine retinal pigment epithelium and choroid, isolated porcine eye melanosomes, and re-pigmented ARPE-19 cells in a dynamic flow system. The experimental studies were supplemented with kinetic simulations. Affinity and capacity of levofloxacin, terazosin, papaverine, and timolol binding to melanin revealed K values of ≈ 50-150 μM and B ≈ 40-112 nmol.mg. The drugs were released from melanin in <1 h (timolol) or in 6-12 h (other drugs). The drugs were released slower from the melanosomes than from melanin; the experimental differences ranged from 1.2-fold (papaverine) to 7.4-fold (timolol). Kinetic simulations supported the role of the melanosomal membrane in slowing down the release of melanin binders. In release studies from the pigmented ARPE-19 cells, drugs were released from the cellular melanin to the extracellular space in ≈ 1 day (timolol) and ≈ 11 days (levofloxacin), i.e., much slower than the release from melanin or melanosomes. Simulations of drug release from pigmented cells in the flow system matched the experimental data and enabled further sensitivity analyses. The simulations demonstrated a significant prolongation of drug retention in the cells as a function of decreasing drug permeability in the melanosomal membranes and increasing melanin content in the cells. Overall, we report the impact of cellular factors in prolonging drug retention and release from melanin-containing cells. These data and simulations will facilitate the design of melanin binding drugs with prolonged ocular actions.
Topics: Animals; Computer Simulation; Levofloxacin; Melanins; Papaverine; Retinal Pigment Epithelium; Swine; Timolol
PubMed: 35738465
DOI: 10.1016/j.jconrel.2022.05.059 -
MBio Feb 2020The fungal human pathogen undergoes melanization in response to nutrient starvation and exposure to exogenous melanin precursors. Melanization protects the fungus...
The fungal human pathogen undergoes melanization in response to nutrient starvation and exposure to exogenous melanin precursors. Melanization protects the fungus against host defense mechanisms such as oxidative damage and other environmental stressors (e.g., heat/cold stress, antimicrobial compounds, ionizing radiation). Conversely, the melanization process generates cytotoxic intermediates, and melanized cells are potentially susceptible to overheating and to certain melanin-binding drugs. Despite the importance of melanin in biology, the signaling mechanisms regulating its synthesis are poorly understood. The recent report by D. Lee, E.-H. Jang, M. Lee, S.-W. Kim, et al. [mBio 10(5):e02267-19, 2019, https://doi.org/10.1128/mBio.02267-19] provides new insights into how regulates melanization. The authors identified a core melanin regulatory network consisting of transcription factors and kinases required for melanization under low-nutrient conditions. The redundant and epistatic connections of this melanin-regulating network demonstrate that melanization is complex and carefully regulated at multiple levels. Such complex regulation reflects the multiple functions of melanin in biology.
Topics: Anti-Infective Agents; Cryptococcosis; Cryptococcus neoformans; Humans; Melanins; Signal Transduction; Transcription Factors
PubMed: 32019794
DOI: 10.1128/mBio.03313-19 -
F1000Research 2020Melanin pigments are responsible for human skin and hair color, and they protect the body from harmful ultraviolet light. The black and brown melanin pigments are... (Review)
Review
Melanin pigments are responsible for human skin and hair color, and they protect the body from harmful ultraviolet light. The black and brown melanin pigments are synthesized in specialized lysosome-related organelles called melanosomes in melanocytes. Mature melanosomes are transported within melanocytes and transferred to adjacent keratinocytes, which constitute the principal part of human skin. The melanosomes are then deposited inside the keratinocytes and darken the skin (a process called tanning). Owing to their dark color, melanosomes can be seen easily with an ordinary light microscope, and melanosome research dates back approximately 150 years; since then, biochemical studies aimed at isolating and purifying melanosomes have been conducted. Moreover, in the last two decades, hundreds of molecules involved in regulating melanosomal functions have been identified by analyses of the genes of coat-color mutant animals and patients with genetic diseases characterized by pigment abnormalities, such as hypopigmentation. In recent years, dynamic analyses by more precise microscopic observations have revealed specific functions of a variety of molecules involved in melanogenesis. This review article focuses on the latest findings with regard to the steps (or mechanisms) involved in melanosome formation and transport of mature melanosomes within epidermal melanocytes. Finally, we will touch on current topics in melanosome research, particularly on the "melanosome transfer" and "post-transfer" steps, and discuss future directions in pigment research.
Topics: Animals; Humans; Keratinocytes; Melanins; Melanocytes; Melanosomes; Skin; Skin Pigmentation
PubMed: 32595944
DOI: 10.12688/f1000research.24625.1