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1.
BMC Oral Health ; 24(1): 451, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38614977

RESUMO

BACKGROUND AND OBJECTIVE: The most frequently seen intra-oral soft tissue is the gingiva. Most often, it is seen as coral-pink tissue that surrounds the neck of the teeth. Gingiva that encircles the tooth necks and covers the alveolar processes of the jaws is an intra-oral tissue that exhibits biomimetic features. The wide range of colors of the gingiva depends on the configuration of gingival vascularity, the degree of epithelial cornification, level of melanogenesis, and the depth of epithelialization. However, the color of the gingiva varies depending on the degree of melanin pigmentation. The current study aimed to identify the different distribution patterns of gingival color and determine the correlation between skin color, gender, and geographical area of origin. MATERIALS AND METHODS: A total of 839 subjects were involved in the study where the gingival color and skin tone were measured using the Dummett-Gupta Oral pigmentation Index (DOPI) combined with VITA VMK MASTER and skin shade method developed by Revlon (USA) and L'Oreal (France) for makeup foundation shades. One investigator was calibrated for the examination of the colors after being tested for normal color vision and color aptitude using the line test. RESULTS: A significant association was found between skin color and gingival pigmentation (χ2 value (6) = 114.48; P = 0.001). It was also found that females (67.1%) significantly had darker gingiva than males (58.3%). The study statistics display that location of the individual was also statistically associated with melanin pigmentation of the gingiva (χ2 value (57) = 559.33; P = 0.001). CONCLUSION: The study concluded that gender, skin color, and individual location are significantly associated with gingival melanin pigmentation.


Assuntos
Doenças da Gengiva , Hiperpigmentação , Feminino , Masculino , Humanos , Gengiva , Melaninas , Pele
2.
Exp Dermatol ; 33(4): e15069, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38568090

RESUMO

Topicals and chemical peels are the standard of care for management of facial hyperpigmentation. However, traditional therapies have come under recent scrutiny, such as topical hydroquinone (HQ) has some regulatory restrictions, and high concentration trichloroacetic acid (TCA) peel pose a risk in patients with skin of colour. The objective of our research was to identify, investigate and elucidate the mechanism of action of a novel TCA- and HQ-free professional-use chemical peel to manage common types of facial hyperpigmentation. Using computational modelling and in vitro assays on tyrosinase, we identified proprietary multi-acid synergistic technology (MAST). After a single application on human skin explants, MAST peel was found to be more effective than a commercial HQ peel in inhibiting melanin (histochemical imaging and gene expression). All participants completed the case study (N = 9) without any adverse events. After administration of the MAST peel by a dermatologist, the scoring and VISIA photography reported improvements in hyperpigmentation, texture and erythema, which could be linked to underlying pathophysiological changes in skin after peeling, visualized by non-invasive optical biopsy of face. Using reflectance confocal microscopy (VivaScope®) and multiphoton tomography (MPTflex™), we observed reduction in melanin, increase in metabolic activity of keratinocytes, and no signs of inflammatory cells after peeling. Subsequent swabbing of the cheek skin found no microbiota dysbiosis resulting from the chemical peel. The strong efficacy with minimum downtime and no adverse events could be linked to the synergistic action of the ingredients in the novel HQ- and TCA-free professional peel technology.


Assuntos
Hidroquinonas , Hiperpigmentação , Melaninas , Humanos , Hiperpigmentação/tratamento farmacológico , Pele , Biologia Computacional , Biópsia
3.
Sci Rep ; 14(1): 8145, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584229

RESUMO

Photoplethysmography (PPG) uses light to detect volumetric changes in blood, and is integrated into many healthcare devices to monitor various physiological measurements. However, an unresolved limitation of PPG is the effect of skin pigmentation on the signal and its impact on PPG based applications such as pulse oximetry. Hence, an in-silico model of the human finger was developed using the Monte Carlo (MC) technique to simulate light interactions with different melanin concentrations in a human finger, as it is the primary determinant of skin pigmentation. The AC/DC ratio in reflectance PPG mode was evaluated at source-detector separations of 1 mm and 3 mm as the convergence rate (Q), a parameter that quantifies the accuracy of the simulation, exceeded a threshold of 0.001. At a source-detector separation of 3 mm, the AC/DC ratio of light skin was 0.472 times more than moderate skin and 6.39 than dark skin at 660 nm, and 0.114 and 0.141 respectively at 940 nm. These findings are significant for the development of PPG-based sensors given the ongoing concerns regarding the impact of skin pigmentation on healthcare devices.


Assuntos
Melaninas , Fotopletismografia , Humanos , Fotopletismografia/métodos , Método de Monte Carlo , Oximetria/métodos , Dedos/fisiologia
4.
J Transl Med ; 22(1): 336, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589876

RESUMO

Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles.


Assuntos
Melanócitos , Medicina Regenerativa , Pigmentação/fisiologia , Melaninas/fisiologia , Folículo Piloso/fisiologia
5.
Biol Sex Differ ; 15(1): 33, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570844

RESUMO

Recent preclinical research exploring how neuropeptide transmitter systems regulate motivated behavior reveal the increasing importance of sex as a critical biological variable. Neuropeptide systems and their central circuits both contribute to sex differences in a range of motivated behaviors and regulate sex-specific behaviors. In this short review, we explore the current research of how sex as a biological variable influences several distinct motivated behaviors that are modulated by the melanin-concentrating hormone (MCH) neuropeptide system. First, we review how MCH regulates feeding behavior within the context of energy homeostasis differently between male and female rodents. Then, we focus on MCH's role in lactation as a sex-specific process within the context of energy homeostasis. Next, we discuss the sex-specific effects of MCH on maternal behavior. Finally, we summarize the role of MCH in drug-motivated behaviors. While these topics are traditionally investigated from different scientific perspectives, in this short review we discuss how these behaviors share commonalities within the larger context of motivated behaviors, and that sex differences discovered in one area of research may impact our understanding in another. Overall, our review highlights the need for further research into how sex differences in energy regulation associated with reproduction and parental care contribute to regulating motivated behaviors.


Assuntos
Hormônios Hipotalâmicos , Melaninas , Neuropeptídeos , Feminino , Masculino , Animais , Caracteres Sexuais , Hormônios Hipotalâmicos/farmacologia , Hormônios Hipotalâmicos/fisiologia , Hormônios Hipofisários/farmacologia , Hormônios Hipofisários/fisiologia
6.
Appl Microbiol Biotechnol ; 108(1): 291, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592509

RESUMO

Melanin is an Aspergillus flavus cell wall component that provides chemical and physical protection to the organism. However, the molecular and biological mechanisms modulating melanin-mediated host-pathogen interaction in A. flavus keratitis are not well understood. This work aimed to compare the morphology, surface proteome profile, and virulence of melanized conidia (MC) and non-melanized conidia (NMC) of A. flavus. Kojic acid treatment inhibited melanin synthesis in A. flavus, and the conidial surface protein profile was significantly different in kojic acid-treated non-melanized conidia. Several cell wall-associated proteins and proteins responsible for oxidative stress, carbohydrate, and chitin metabolic pathways were found only in the formic acid extracts of NMC. Scanning electron microscopy (SEM) analysis showed the conidial surface morphology difference between the NMC and MC, indicating the role of melanin in the structural integrity of the conidial cell wall. The levels of calcofluor white staining efficiency were different, but there was no microscopic morphology difference in lactophenol cotton blue staining between MC and NMC. Evaluation of the virulence of MC and NMC in the Galleria mellonella model showed NMC was less virulent compared to MC. Our findings showed that the integrity of the conidial surface is controlled by the melanin layer. The alteration in the surface protein profile indicated that many surface proteins are masked by the melanin layer, and hence, melanin can modulate the host response by preventing the exposure of fungal proteins to the host immune defense system. The G. mellonella virulence assay also confirmed that the NMC were susceptible to host defense as in other Aspergillus pathogens. KEY POINTS: • l-DOPA melanin production was inhibited in A. flavus isolates by kojic acid, and for the first time, scanning electron microscopy (SEM) analysis revealed morphological differences between MC and NMC of A. flavus strains • Proteome profile of non-melanized conidia showed more conidial surface proteins and these proteins were mainly involved in the virulence, oxidative stress, and metabolism pathways • Non-melanized conidia of A. flavus strains were shown to be less virulent than melanised conidia in an in vivo virulence experiment with the G. melonella model.


Assuntos
Melaninas , Proteínas de Membrana , Aspergillus flavus , Esporos Fúngicos , Proteoma , Virulência
7.
Biochem Biophys Res Commun ; 710: 149917, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38604071

RESUMO

Melanin-concentrating hormone (MCH) receptor 1 (MCHR1), a G protein-coupled receptor, is poised for interaction with its ligands on the plasma membrane. Analyses of MCHR1 knockout mice suggest that this receptor could be a therapeutic target for the treatment of appetite disorders, glucose metabolism, psychiatric disorders, and inflammation. Binding of MCH to MCHR1 initiates calcium signaling, which is subsequently attenuated through receptor internalization. However, the ultimate destiny of the receptor post-internalization remains unexplored. In this study, we report the extracellular secretion of MCHR1 via exosomes. The recruitment of MCHR1 to exosomes occurs subsequent to its internalization, which is induced by stimulation with the ligand MCH. Although a highly glycosylated form of MCHR1, potentially representing a mature form, is selectively recruited to exosomes, the MCHR1 transferred into other cells does not exhibit functionality. The truncation of MCHR1 at the C-terminus not only impairs its response to MCH but also hinders its recruitment to exosomes. These findings imply that functional MCHR1 could be secreted extracellularly via exosomes, a process that may represent a mechanism for the termination of intracellular MCHR1 signaling.


Assuntos
Exossomos , Hormônios Hipotalâmicos , Receptores do Hormônio Hipofisário , Humanos , Camundongos , Animais , Exossomos/metabolismo , Receptores do Hormônio Hipofisário/metabolismo , Transdução de Sinais , Camundongos Knockout , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Melaninas/metabolismo
8.
Proc Natl Acad Sci U S A ; 121(16): e2321323121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38607931

RESUMO

Extracellular vesicles (EVs) facilitate the transfer of proteins, lipids, and genetic material between cells and are recognized as an additional mechanism for sustaining intercellular communication. In the epidermis, the communication between melanocytes and keratinocytes is tightly regulated to warrant skin pigmentation. Melanocytes synthesize the melanin pigment in melanosomes that are transported along the dendrites prior to the transfer of melanin pigment to keratinocytes. EVs secreted by keratinocytes modulate pigmentation in melanocytes [(A. Lo Cicero et al., Nat. Commun. 6, 7506 (2015)]. However, whether EVs secreted by keratinocytes contribute to additional processes essential for melanocyte functions remains elusive. Here, we show that keratinocyte EVs enhance the ability of melanocytes to generate dendrites and mature melanosomes and promote their efficient transfer. Further, keratinocyte EVs carrying Rac1 induce important morphological changes, promote dendrite outgrowth, and potentiate melanin transfer to keratinocytes. Hence, in addition to modulating pigmentation, keratinocytes exploit EVs to control melanocyte plasticity and transfer capacity. These data demonstrate that keratinocyte-derived EVs, by regulating melanocyte functions, are major contributors to cutaneous pigmentation and expand our understanding of the mechanism underlying skin pigmentation via a paracrine EV-mediated communication.


Assuntos
Vesículas Extracelulares , Melanossomas , Melaninas , Melanócitos , Queratinócitos
9.
Molecules ; 29(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611771

RESUMO

To explore the composition of anthocyanins and expand their biological activities, anthocyanins were systematically isolated and purified from tubers of Solanum tuberosum L., and their tyrosinase inhibitory activity was investigated. In this study, two new anthocyanin degradation compounds, norpetanin (9) and 4-O-(p-coumaryl) rhamnose (10), along with 17 known anthocyanins and their derivatives, were isolated and purified from an acid-ethanolic extract of fresh purple potato tubers. Their structures were elucidated via 1D and 2D NMR and HR-ESI-MS and compared with those reported in the literature. The extracts were evaluated for anthocyanins and their derivatives using a tyrosinase inhibitor screening kit and molecular docking technology, and the results showed that petanin, norpetanin, 4-O-(p-coumaryl) rhamnose, and lyciruthephenylpropanoid D/E possessed tyrosinase inhibitory activity, with 50% inhibiting concentration (IC50) values of 122.37 ± 8.03, 115.53 ± 7.51, 335.03 ± 12.99, and 156.27 ± 11.22 µM (Mean ± SEM, n = 3), respectively. Furthermore, petanin was validated against melanogenesis in zebrafish; it was found that it could significantly inhibit melanin pigmentation (p < 0.001), and the inhibition rate of melanin was 17% compared with the normal group. This finding may provide potential treatments for diseases with abnormal melanin production, and high-quality raw materials for whitening cosmetics.


Assuntos
Antocianinas , Solanum tuberosum , Animais , Antocianinas/farmacologia , Monofenol Mono-Oxigenase , Melaninas , Simulação de Acoplamento Molecular , Ramnose , Peixe-Zebra
10.
Int J Mol Sci ; 25(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38612421

RESUMO

The retinal pigment epithelium (RPE), which ensures the normal functioning of the neural retina, is a pigmented single-cell layer that separates the retina from the Bruch's membrane and the choroid. There are three main types of pigment granules in the RPE cells of the human eye: lipofuscin granules (LG) containing the fluorescent "age pigment" lipofuscin, melanoprotein granules (melanosomes, melanolysosomes) containing the screening pigment melanin and complex melanolipofuscin granules (MLG) containing both types of pigments simultaneously-melanin and lipofuscin. This review examines the functional role of pigment granules in the aging process and in the development of oxidative stress and associated pathologies in RPE cells. The focus is on the process of light-induced oxidative degradation of pigment granules caused by reactive oxygen species. The reasons leading to increased oxidative stress in RPE cells as a result of the oxidative degradation of pigment granules are considered. A mechanism is proposed to explain the phenomenon of age-related decline in melanin content in RPE cells. The essence of the mechanism is that when the lipofuscin part of the melanolipofuscin granule is exposed to light, reactive oxygen species are formed, which destroy the melanin part. As more melanolipofuscin granules are formed with age and the development of degenerative diseases, the melanin in pigmented epithelial cells ultimately disappears.


Assuntos
Melaninas , Epitélio Pigmentado da Retina , Humanos , Lipofuscina , Espécies Reativas de Oxigênio , Retina
11.
Pestic Biochem Physiol ; 200: 105810, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582582

RESUMO

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive tea pest in China. Mimesis, characterized by changing body color, is an important trait of E. grisescens larvae. Hence, identifying melanin pathway-related genes may contribute to developing new pest control strategies. In the present study, we cloned Egebony, a gene potentially involved in melanin pigmentation in E. grisescens, and subsequently conducted CRISPR/Cas9-mediated targeted mutagenesis of Egebony to analyze its role in pigmentation and development. At the larvae, prepupae, and pupae stages, Egebony-knockout individuals exhibited darker pigmentation than the wild-type. However, Egebony knockout did not impact the colors of sclerotized appendants, including ocelli, setae, and claws. While mutant pupae could successfully develop into moths, they were unable to emerge from the puparium. Notably, embryo hatchability and larval survival of mutants remained normal. Further investigation indicated that mutant pupae exhibited significantly stronger shearing force than the wild-type, with the pigmented layer of mutant pupae appearing darker and thicker. Collectively, these results suggest that the loss of Egebony might increase the rigidity of the puparium and prevent moth eclosion. This study provides new insights into understanding the function and diversification of ebony in insect development and identifies a lethal gene that can be manipulated for developing effective pest control strategies.


Assuntos
Mariposas , Animais , Mariposas/genética , Melaninas/genética , Sistemas CRISPR-Cas , Larva/genética , Pigmentação/genética
12.
Georgian Med News ; (346): 14-20, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38501615

RESUMO

In neurodegenerative diseases, particularly in Parkinson's disease (PD), antinociceptive centers are often implicated in neurodegeneration, leading to persistent pain unresponsive to narcotic substances. This study investigated the periaqueductal gray matter (PAG) and the nucleus raphe magnus (NRM), components of the brain's antinociceptive system. In conditions of rotenone intoxication (an experimental PD model), morphological changes in intracellular structures were observed in PAG and NRM neurons, indicating metabolic disorders characteristic of PD (alterations in the shape and size of neuronal bodies and processes, disruption of acid phosphatase activity in neuron cytoplasm). Under the influence of bacterial melanin and in combination with synoestrol, positive changes in structural properties were observed in PAG and NRM neurons compared to the rotenone model of PD. This included the preservation of the morphological characteristics typical of these brain regions, with cells exhibiting shapes and sizes close to normal. Furthermore, under the influence of these therapeutic agents, an increase in phosphatase activity in cell cytoplasm was detected, indicating an acceleration of metabolic processes (metabolic activation) disrupted by rotenone intoxication. The data obtained suggests that bacterial melanin and synoestrol may act as potential neuroprotective agents against PAG and NRM neurons in the rat brain in the rotenone model of PD. Further research is needed to elucidate the mechanisms of action of therapeutic doses and propose their use in the treatment of PD, either in isolation or combination therapy.


Assuntos
Doença de Parkinson , Núcleos da Rafe , Animais , Núcleos da Rafe/fisiologia , Doença de Parkinson/tratamento farmacológico , Rotenona/farmacologia , Rotenona/análise , Melaninas/análise , Analgésicos
13.
J Am Chem Soc ; 146(11): 7222-7232, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38469853

RESUMO

Defect centers in a nanodiamond (ND) allow the detection of tiny magnetic fields in their direct surroundings, rendering them as an emerging tool for nanoscale sensing applications. Eumelanin, an abundant pigment, plays an important role in biology and material science. Here, for the first time, we evaluate the comproportionation reaction in eumelanin by detecting and quantifying semiquinone radicals through the nitrogen-vacancy color center. A thin layer of eumelanin is polymerized on the surface of nanodiamonds (NDs), and depending on the environmental conditions, such as the local pH value, near-infrared, and ultraviolet light irradiation, the radicals form and react in situ. By combining experiments and theoretical simulations, we quantify the local number and kinetics of free radicals in the eumelanin layer. Next, the ND sensor enters the cells via endosomal vesicles. We quantify the number of radicals formed within the eumelanin layer in these acidic compartments by applying optical relaxometry measurements. In the future, we believe that the ND quantum sensor could provide valuable insights into the chemistry of eumelanin, which could contribute to the understanding and treatment of eumelanin- and melanin-related diseases.


Assuntos
Melaninas , Nanodiamantes , Raios Ultravioleta , Radicais Livres
14.
Int J Biol Macromol ; 265(Pt 2): 130983, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38521304

RESUMO

The development of environmentally friendly multifunctional auxiliaries for textile modification is the focus of attention in textile industry in recent years. Polydopamine is an important biological macromolecule and widely used in biomedicine, nanomaterials, material surface modification and other fields. In this study, the novel multifunctional melanin-like nanoparticles (Nha-PDA NPs) were prepared and used for antibacterial, hydrophobic, and UV protective of textiles. Nha-PDA NPs were prepared with dopamine (DA) and n-hexylamine (Nha) by simple autoxidation copolymerization. Nha-PDA NPs were bound to the fabric surface through the PDA structure in Nha-PDA NPs that has been widely confirmed to have strong adhesion on the surface of many materials. The modified fabrics, Nha-PDA NPs@Cotton, had good hydrophobic, antibacterial and UV protective properties. The static water contact angles of the modified fabrics could reach 120°. The antibacterial rates of Nha-PDA NPs@Cotton against E. coli and S. aureus were above 85 %. The maximum UPF value of the modified cotton was 362, indicating that the ultraviolet protection performance was excellent. The fabric modified with multifunctional melanin-like nanoparticle provides a green way for the multifunctional modification of textiles.


Assuntos
Escherichia coli , Indóis , Melaninas , Polímeros , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Têxteis , Gossypium
15.
ACS Appl Bio Mater ; 7(4): 2186-2196, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38466818

RESUMO

Eumelanin is a natural pigment that can be particularly valuable for sustainable bioelectronic devices due to its inherent biocompatibility and hydration-dependent conductivity. However, the low conductivity of eumelanin limits its technological development. In this research, electrochemical doping was proposed as an alternative route to increase the electronic conductivity of synthetic eumelanin derivatives. Thin films of sulfonated eumelanin were deposited on platinum interdigitated electrodes and electrochemically treated by using cyclic voltammetry and chronoamperometry treatments. X-ray photoelectron spectroscopy analysis confirmed ion doping in sulfonated melanin. Current-voltage, current-time, and electrochemical impedance measurements were used to investigate the effect of different aqueous electrolytes (including KCl and LiClO4) treatments on the charge transport of sulfonated eumelanin. We show that the conductivity depends on the type and size of the anion used and can reach 10-3 S·cm-1. Additionally, depending on the electrolyte, there is a change in charge transport from mixed ionic/electronic to a predominantly electronic-only conduction. Our results show that the chemical nature of the ion plays an important role in the electrochemical doping and, consequently, in the charge transport of eumelanin. These insights serve as inspiration to explore the use of alternative electrolytes with different compositions further and develop eumelanin-based devices with tunable conductivities.


Assuntos
Alcanossulfonatos , Melaninas , Condutividade Elétrica , Eletrônica , Eletrólitos
16.
Pharm Biol ; 62(1): 296-313, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38555860

RESUMO

CONTEXT: Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options. OBJECTIVE: This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms. MATERIALS AND METHODS: We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD's hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an in vitro hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting. RESULTS: ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC50) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells. DISCUSSION AND CONCLUSION: THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.


Assuntos
Medicamentos de Ervas Chinesas , Hiperpigmentação , Humanos , Análise da Randomização Mendeliana , Melaninas , Monofenol Mono-Oxigenase , Simulação de Acoplamento Molecular , alfa-MSH , Farmacologia em Rede , Interleucina-6 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperpigmentação/tratamento farmacológico
17.
Int J Mol Sci ; 25(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38542347

RESUMO

Tyrosinase serves as the key enzyme in melanin biosynthesis, catalyzing the initial steps of the pathway, the hydroxylation of the amino acid L-tyrosine into L-3,4-dihydroxyphenylalanine (L-DOPA), followed by the subsequent oxidation of L-DOPA into dopaquinone (DQ), and it facilitates the conversion of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into 5,6-indolequinone-2-carboxylic acid (IQCA) and 5,6-dihydroxy indole (DHI) into indolequinone (IQ). Despite its versatile substrate capabilities, the precise mechanism underlying tyrosinase's multi-substrate activity remains unclear. Previously, we expressed, purified, and characterized the recombinant intra-melanosomal domain of human tyrosinase (rTyr). Here, we demonstrate that rTyr mimics native human tyrosinase's catalytic activities in vitro and in silico. Molecular docking and molecular dynamics (MD) simulations, based on rTyr's homology model, reveal variable durability and binding preferences among tyrosinase substrates and products. Analysis of root mean square deviation (RMSD) highlights the significance of conserved residues (E203, K334, F347, and V377), which exhibit flexibility during the ligands' binding. Additionally, in silico analysis demonstrated that the OCA1B-related P406L mutation in tyrosinase substantially influences substrate binding, as evidenced by the decreased number of stable ligand conformations. This correlation underscores the mutation's impact on substrate docking, which aligns with the observed reduction in rTyr activity. Our study highlights how rTyr dynamically adjusts its structure to accommodate diverse substrates and suggests a way to modulate rTyr ligand plasticity.


Assuntos
Indolquinonas , Monofenol Mono-Oxigenase , Humanos , Monofenol Mono-Oxigenase/metabolismo , Melaninas/metabolismo , Levodopa , Simulação de Acoplamento Molecular , Ligantes
18.
Lasers Surg Med ; 56(4): 361-370, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38506244

RESUMO

BACKGROUND: Limited research exists on laser treatment of giant congenital melanocytic nevus (GCMN). OBJECTIVE: We sought to elucidate the efficacy of the Erbium: YAG laser on GCMN and the histologic factors associated with a positive clinical response. METHODS AND MATERIALS: Between 2019 and 2022, we enrolled 30 medium-to-giant CMN patients who underwent Er: YAG laser treatment. All patients received biopsies before and after laser treatments. Clinical efficacy outcomes were evaluated by the investigator's global assessment (IGA), 5-point scale of depigmentation, and Vancouver Scar Scale (VSS) scores at least 6 months after treatment. RESULTS: Of the 30 cases, 18 (60.0%) showed improvement (IGA score ≥3). Eight (26.7%) patients showed repigmentation. Eight (26.7%) patients developed hypertrophic scars. The average IGA, depigmentation, and VSS scores were 2.93, 3.57, and 3.20. The IGA score was higher (3.24 ± 1.18 vs. 2.22 ± 0.97, p = 0.031) and a lower repigmentation rate (14.3% vs. 55.6%, p = 0.032) was observed in the cases with Grenz zone. The IGA score was higher (3.33 ± 1.24 vs. 2.13 ± 0.89, p = 0.023) and the repigmentation rate was lower (11.1% vs. 50.0%, p = 0.034) also in the cases with the melanocytes nests with aggregation of melanin. Lesions with superficial ablation resulted in less hypertrophic scar formation than those with deep ablation (5.9% vs. 53.8%, p < 0.05). CONCLUSION: The Er: YAG laser demonstrated effective clinical results for GCMNs. The grenz zone and the melanocytes nests with aggregation of melanin are promising predictors of laser efficacy.


Assuntos
Cicatriz Hipertrófica , Terapia a Laser , Lasers de Estado Sólido , Nevo Pigmentado , Neoplasias Cutâneas , Humanos , Érbio , Melaninas , Lasers de Estado Sólido/uso terapêutico , Terapia a Laser/métodos , Resultado do Tratamento , Nevo Pigmentado/radioterapia , Nevo Pigmentado/cirurgia , Cicatriz Hipertrófica/patologia , Imunoglobulina A
19.
Neuroimage ; 291: 120588, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38537765

RESUMO

BACKGROUND: Parkinson's disease (PD) is associated with the loss of neuromelanin (NM) and increased iron in the substantia nigra (SN). Magnetization transfer contrast (MTC) is widely used for NM visualization but has limitations in brain coverage and scan time. This study aimed to develop a new approach called Proton-density Enhanced Neuromelanin Contrast in Low flip angle gradient echo (PENCIL) imaging to visualize NM in the SN. METHODS: This study included 30 PD subjects and 50 healthy controls (HCs) scanned at 3T. PENCIL and MTC images were acquired. NM volume in the SN pars compacta (SNpc), normalized image contrast (Cnorm), and contrast-to-noise ratio (CNR) were calculated. The change of NM volume in the SNpc with age was analyzed using the HC data. A group analysis compared differences between PD subjects and HCs. Receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculations were used to evaluate the diagnostic performance of NM volume and CNR in the SNpc. RESULTS: PENCIL provided similar visualization and structural information of NM compared to MTC. In HCs, PENCIL showed higher NM volume in the SNpc than MTC, but this difference was not observed in PD subjects. PENCIL had higher CNR, while MTC had higher Cnorm. Both methods revealed a similar pattern of NM volume in SNpc changes with age. There were no significant differences in AUCs between NM volume in SNpc measured by PENCIL and MTC. Both methods exhibited comparable diagnostic performance in this regard. CONCLUSIONS: PENCIL imaging provided improved CNR compared to MTC and showed similar diagnostic performance for differentiating PD subjects from HCs. The major advantage is PENCIL has rapid whole-brain coverage and, when using STAGE imaging, offers a one-stop quantitative assessment of tissue properties.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Parte Compacta da Substância Negra , Imageamento por Ressonância Magnética/métodos , Melaninas
20.
Lasers Surg Med ; 56(4): 337-345, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38436118

RESUMO

OBJECTIVES: Subcutaneous mastectomy is a crucial component of gender affirmation therapy for transgender men (TM), but the scars that result from this procedure can frequently impair their quality of life. This study aimed to assess the efficacy and safety of 1064-nm fractional picosecond laser (FxPico) treatment for hypertrophic and atrophic postmastectomy scars in TM. METHODS: Twenty-two patients with a total of 35 pairs of bilateral symmetric mastectomy scars were enrolled. One of each pair of symmetric scars was randomly assigned to receive four FxPico treatments at 4-week intervals. All scars were evaluated using the modified Vancouver Scar Scale (mVSS) and three-dimensional imaging for scar roughness, melanin index, and hemoglobin index before each treatment session and at 1, 3, and 6 months following the last treatment. Additionally, participant-rated scar satisfaction (PSS) and scar improvement (Global Assessment Score, GAS), as well as adverse events were recorded. RESULTS: During the 6-month follow-up period after the end of laser treatment sessions, the treated scars showed significant reductions in the mVSS compared to the untreated controls (p < 0.001), whereas the melanin index and hemoglobin index were not significantly different. Subgroup analysis of hypertrophic scars demonstrated statistically significant reductions in mVSS at 1 (p = 0.003) and 3 months (p = 0.041) after the end of laser treatments. PSS was significantly higher on the laser-treated scars than the controls (p = 0.008), and a participant-rated GAS of 2.95 ± 0.65 was found. There were no serious adverse events reported. CONCLUSIONS: 1064-nm FxPico could be utilized to treat mastectomy scars among TM, particularly the hypertrophic type.


Assuntos
Neoplasias da Mama , Cicatriz Hipertrófica , Lasers de Gás , Pessoas Transgênero , Masculino , Humanos , Cicatriz/etiologia , Cicatriz/radioterapia , Cicatriz/cirurgia , Neoplasias da Mama/cirurgia , Qualidade de Vida , Melaninas , Resultado do Tratamento , Mastectomia , Cicatriz Hipertrófica/patologia , Lasers , Hipertrofia/cirurgia , Hemoglobinas
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