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Brain and Behavior Jun 2024Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations...
INTRODUCTION
Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin-sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin-a by-product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward-related processes, may provide critical insights into reward circuit function in AN.
METHODS
This study will incorporate neuromelanin-sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight-restored AN (N = 30), and age-matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin-sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning.
CONCLUSION
This study will be among the first to interrogate midbrain neuromelanin in AN-a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.
Topics: Humans; Reward; Melanins; Anorexia Nervosa; Mesencephalon; Magnetic Resonance Imaging; Female; Adult; Young Adult; Adolescent; Male; Pre-Registration Publication
PubMed: 38898625
DOI: 10.1002/brb3.3573 -
Aesthetic Plastic Surgery Jun 2024Our meta-analysis indicated favorable results in improving scar hyperpigmentation through fat grafting, but there remains a need for further investigation using...
Our meta-analysis indicated favorable results in improving scar hyperpigmentation through fat grafting, but there remains a need for further investigation using objective measures to validate these clinical findings and elucidate the underlying mechanisms. Current evidence from animal studies showed that fat grafting may exert its beneficial effects on scar hyperpigmentation through complex cellular and molecular pathways involving the regulation of melanin synthesis and skin remodeling. However, interpretation can be influenced by various factors, highlighting the importance of integrating multiple lines of evidence to draw robust conclusions.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PubMed: 38898244
DOI: 10.1007/s00266-024-04165-0 -
Annals of Plastic Surgery Jun 2024Hyperpigmentation is a skin disorder characterized by a localized darkening of the skin due to increased melanin production. When patients fail first line topical...
BACKGROUND
Hyperpigmentation is a skin disorder characterized by a localized darkening of the skin due to increased melanin production. When patients fail first line topical treatments, secondary treatments such as chemical peels and lasers are offered. However, these interventions are not devoid of risks and are associated with postinflammatory hyperpigmentation. In the quest for novel therapeutic potentials, this study aims to investigate computational methods in the identification of new targeted therapies in the treatment of hyperpigmentation.
METHODS
We used a comprehensive approach, which integrated text mining, interpreting gene lists through enrichment analysis and integration of diverse biological information (GeneCodis), protein-protein association networks and functional enrichment analyses (STRING), and plug-in network centrality parameters (Cytoscape) to pinpoint genes closely associated with hyperpigmentation. Subsequently, analysis of drug-gene interactions to identify potential drugs (Cortellis) was utilized to select drugs targeting these identified genes. Lastly, we used Deep Learning Based Drug Repurposing Toolkit (DeepPurpose) to conduct drug-target interaction predictions to ultimately identify candidate drugs with the most promising binding affinities.
RESULTS
Thirty-four hyperpigmentation-related genes were identified by text mining. Eight key genes were highlighted by utilizing GeneCodis, STRING, Cytoscape, gene enrichment, and protein-protein interaction analysis. Thirty-five drugs targeting hyperpigmentation-associated genes were identified by Cortellis, and 29 drugs, including 16 M2PK1 inhibitors, 11 KRAS inhibitors, and 2 BRAF inhibitors were recommended by DeepPurpose.
CONCLUSIONS
The study highlights the promise of advanced computational methodology for identifying potential treatments for hyperpigmentation.
PubMed: 38896860
DOI: 10.1097/SAP.0000000000004007 -
Frontiers in Chemistry 2024Tyrosinase is one important rate limiting enzyme in melanin synthesis, directly affecting the melanin synthesis. Quercetagetin is one active ingredient from marigold....
Tyrosinase is one important rate limiting enzyme in melanin synthesis, directly affecting the melanin synthesis. Quercetagetin is one active ingredient from marigold. Thence, the inhibition effects of quercetagetin against tyrosinase were investigated. The results showed quercetagetin could inhibit tyrosinase activity with IC value of 0.19 ± 0.01 mM and the inhibition type was a reversible mixed-type. Results of fluorescence quenching showed quercetagetin could quench tyrosinase fluorescence in static process. CD and 3D fluorescence results showed the interaction of quercetagetin to tyrosinase could change tyrosinase conformation to inhibit activity. Moreover, docking revealed details of quercetagetin's interactions with tyrosinase.
PubMed: 38894729
DOI: 10.3389/fchem.2024.1411801 -
Molecules (Basel, Switzerland) May 2024This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of , and to evaluate their inhibitory effects on melanogenesis in B16F10 murine...
This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of , and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of , indicating their promising role as natural agents for skin lightening.
Topics: Resveratrol; Plant Extracts; Animals; Mice; Melanins; Stilbenes; Melanoma, Experimental; Cell Line, Tumor; Monophenol Monooxygenase; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Melanogenesis
PubMed: 38893349
DOI: 10.3390/molecules29112473 -
International Journal of Molecular... Jun 2024The skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson's disease and many others. Recent... (Review)
Review
The skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson's disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly and indirectly regulate behaviour. Conversely, CNS-driven neural and hormonal responses have been demonstrated to regulate pigmentation, e.g., under stress. Additionally, due to the shared neuroectodermal origins of the melanocytes and neurons in the CNS, certain CNS diseases may be linked to pigmentation-related changes due to common regulators, e.g., MC1R variations. Furthermore, the HPA analogue of the skin connects skin pigmentation to the endocrine system, thereby allowing the skin to index possible hormonal abnormalities visibly. In this review, insight is provided into skin pigment production and neuromelanin synthesis in the brain and recent findings are summarised on how signalling pathways in the skin, with a particular focus on pigmentation, are interconnected with the central nervous system. Thus, this review may supply a better understanding of the mechanism of several skin-brain associations in health and disease.
Topics: Humans; Skin Pigmentation; Brain; Animals; Skin; Ultraviolet Rays; Melanins; Signal Transduction; Behavior
PubMed: 38892387
DOI: 10.3390/ijms25116199 -
International Journal of Molecular... May 2024Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism...
Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism remains unclear. Therefore, to investigate the underlying mechanism of petanin's anti-melanogenic effects, the enzyme activity, protein expression and mRNA transcription of melanogenic and related signaling pathways in zebrafish using network pharmacology, molecular docking and molecular dynamics simulation were combined for analysis. The results showed that petanin could inhibit tyrosinase activity and melanogenesis, change the distribution and arrangement of melanocytes and the structure of melanosomes, reduce the activities of catalase (CAT) and peroxidase (POD) and enhance the activity of glutathione reductase (GR). It also up-regulated JNK phosphorylation, inhibited ERK/RSK phosphorylation and down-regulated CREB/MITF-related protein expression and mRNA transcription. These results were consistent with the predictions provided through network pharmacology and molecular docking. Thus, petanin could inhibit the activity of tyrosinase and the expression of tyrosinase by inhibiting and negatively regulating the tyrosinase-related signaling pathway ERK/CREB/MITF through p-JNK. In conclusion, petanin is a good tyrosinase inhibitor and anti-melanin natural compound with significant market prospects in melanogenesis-related diseases and skin whitening cosmetics.
Topics: Animals; Zebrafish; Melanins; Molecular Docking Simulation; Phosphorylation; MAP Kinase Signaling System; Signal Transduction; Cyclic AMP Response Element-Binding Protein; Monophenol Monooxygenase; Microphthalmia-Associated Transcription Factor; Melanocytes
PubMed: 38892131
DOI: 10.3390/ijms25115939 -
International Journal of Molecular... May 2024This study presents the effects of treating polystyrene (PS) cell culture plastic with oxidoreductase enzyme laccase and the catechol substrates caffeic acid (CA),...
Laccase-Treated Polystyrene Surfaces with Caffeic Acid, Dopamine, and L-3,4-Dihydroxyphenylalanine Substrates Facilitate the Proliferation of Melanocytes and Embryonal Carcinoma Cells NTERA-2.
This study presents the effects of treating polystyrene (PS) cell culture plastic with oxidoreductase enzyme laccase and the catechol substrates caffeic acid (CA), L-DOPA, and dopamine on the culturing of normal human epidermal melanocytes (NHEMs) and human embryonal carcinoma cells (NTERA-2). The laccase-substrate treatment improved PS hydrophilicity and roughness, increasing NHEM and NTERA-2 adherence, proliferation, and NHEM melanogenesis to a level comparable with conventional plasma treatment. Cell adherence dynamics and proliferation were evaluated. The NHEM endpoint function was quantified by measuring melanin content. PS surfaces treated with laccase and its substrates demonstrated the forming of polymer-like structures. The surface texture roughness gradient and the peak curvature were higher on PS treated with a combination of laccase and substrates than laccase alone. The number of adherent NHEM and NTERA-2 was significantly higher than on the untreated surface. The proliferation of NHEM and NTERA-2 correspondingly increased on treated surfaces. NHEM melanin content was enhanced 6-10-fold on treated surfaces. In summary, laccase- and laccase-substrate-modified PS possess improved PS surface chemistry/hydrophilicity and altered roughness compared to untreated and plasma-treated surfaces, facilitating cellular adherence, subsequent proliferation, and exertion of the melanotic phenotype. The presented technology is easy to apply and creates a promising custom-made, substrate-based, cell-type-specific platform for both 2D and 3D cell culture.
Topics: Humans; Laccase; Melanocytes; Cell Proliferation; Polystyrenes; Caffeic Acids; Dopamine; Melanins; Cell Adhesion; Levodopa; Surface Properties; Cell Line, Tumor; Embryonal Carcinoma Stem Cells
PubMed: 38892114
DOI: 10.3390/ijms25115927 -
International Journal of Molecular... May 2024Nanotechnology is revolutionizing fields of high social and economic impact. such as human health preservation, energy conversion and storage, environmental... (Review)
Review
Nanotechnology is revolutionizing fields of high social and economic impact. such as human health preservation, energy conversion and storage, environmental decontamination, and art restoration. However, the possible global-scale application of nanomaterials is raising increasing concerns, mostly related to the possible toxicity of materials at the nanoscale. The possibility of using nanomaterials in cosmetics, and hence in products aimed to be applied directly to the human body, even just externally, is strongly debated. Preoccupation arises especially from the consideration that nanomaterials are mostly of synthetic origin, and hence are often seen as "artificial" and their effects as unpredictable. Melanin, in this framework, is a unique material since in nature it plays important roles that specific cosmetics are aimed to cover, such as photoprotection and hair and skin coloration. Moreover, melanin is mostly present in nature in the form of nanoparticles, as is clearly observable in the ink of some animals, like cuttlefish. Moreover, artificial melanin nanoparticles share the same high biocompatibility of the natural ones and the same unique chemical and photochemical properties. Melanin is hence a natural nanocosmetic agent, but its actual application in cosmetics is still under development, also because of regulatory issues. Here, we critically discuss the most recent examples of the application of natural and biomimetic melanin to cosmetics and highlight the requirements and future steps that would improve melanin-based cosmetics in the view of future applications in the everyday market.
Topics: Melanins; Humans; Hair Color; Animals; Cosmetics; Nanoparticles; Skin Pigmentation; Nanostructures; Nanotechnology
PubMed: 38892049
DOI: 10.3390/ijms25115862 -
Chirality Jun 2024Chirality plays a fundamental role in natural phenomena, yet its manifestation on solid surfaces remains relatively unexplored. In this study, we investigate the...
Chirality plays a fundamental role in natural phenomena, yet its manifestation on solid surfaces remains relatively unexplored. In this study, we investigate the formation of chiroptical melanin-based self-assembled films on quartz substrates, leveraging mussel-inspired surface chemistry. Water-soluble porphyrins serve as molecular synthons, facilitating the spontaneous formation of hetero-aggregates in phosphate-buffered saline containing L- or D-DOPA. Spectroscopic analysis reveals chiral transfer from DOPA enantiomers to porphyrin hetero-aggregates, followed by the disruption of these latter and subsequent generation of chiral melanin structures in solution. Quartz substrates inserted into these solutions spontaneously accumulate homogeneous melanin-like films over days, demonstrating the feasibility of self-assembly. The resulting films exhibit characteristic UV/Vis and CD spectra, with distinct signals indicating successful chiral induction. Interestingly, the AFM characterizations reveal a distinct surface morphology, and in addition, some thermal and mechanical properties have been taken into account. Overall, this study sheds light on the formation, stability, and chiroptical properties of melanin-based films, paving the way for their application in various fields.
PubMed: 38890151
DOI: 10.1002/chir.23695