A Novel Method for Visualizing Melanosome and Melanin Distribution in Human Skin Tissues

Melanin incorporated into keratinocytes plays an important role in photoprotection; however, abnormal melanin accumulation causes hyperpigmentary disorders. To understand the mechanism behind the accumulation of excess melanin in the skin, it is essential to clarify the spatial distribution of melanosomes or melanin in the epidermis. Although several markers have been used to detect melanosomes or melanin, no suitable markers to determine the precise localization of melanin in the epidermis have been reported. In this study, we showed that melanocore-interacting Kif1c-tail (M-INK), a recently developed fluorescent probe for visualizing mature melanosomes, binds to purified melanin in vitro, and applied it for detecting melanin in human skin tissues. Frozen skin sections from different phototypes were co-stained for the hemagglutinin (HA)-tagged M-INK probe and markers of melanocytes or keratinocytes, and a wide distribution of melanin was observed in the epidermis. Analysis of the different skin phototypes indicated that the fluorescent signals of HA-M-INK correlated well with skin color. The reconstruction of three-dimensional images of epidermal sheets enabled us to observe the spatial distribution of melanin in the epidermis. Thus, the HA-M-INK probe is an ideal tool to individually visualize melanin (or melanosome) distribution in melanocytes and in keratinocytes in skin tissues.     

Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication

Skin pigmentation can occur due to increased melanin, including melanocyte proliferation, melanin biosynthesis, or melanocyte migration. There are many factors that influence the melanin production process, but the role of neurotransmitters in this process is still unclear. We found that histamine and serotonin influence the different stages of melanogenesis and melanogenesis, which increase melanogenesis. Since then, several related papers have been published, and from these papers, it has been recognised that the role of neurotransmitters in skin-pigment-related diseases needs to be summarised. By introducing the role of neurotransmitters in the regulation of various pigment disorders, including vitiligo and melasma, through this review, many researchers can be expected to try to apply neurotransmitter-related agonists and antagonists as treatments for skin pigment disorders.     

Development of Pigmentation-Regulating Agents by Drug Repositioning

Skin color is determined by the processes of melanin synthesis and distribution. Problems in various molecules or signaling pathways involved in melanin synthesis contribute to skin pigmentation defects. Several trials have been conducted on the production of pigmentation-regulating agents, and drug repositioning has emerged as a modern technique to identify new uses for existing drugs. Our research team has researched substances or drugs associated with pigmentation control and, as a result, nilotinib, sorafenib, and ICG-001 have been found to promote pigmentation, while 5-iodotubercidin inhibits pigmentation. Therefore, these substances or medications were suggested as potential therapeutics for pigmentation disorders by drug repositioning.     

LATS1 Is a Mediator of Melanogenesis in Response to Oxidative Stress and Regulator of Melanoma Growth

The LATS1 kinase has been described as a tumor suppressor in various cancers. However, its role in melanoma has not been fully elucidated. There are several processes involved in tumorigenesis, including melanin production. Melanin content positively correlates with the level of reactive oxygen species (ROS) inside the cell. Accordingly, the purpose of the study was to assess the role of LATS1 in melanogenesis and oxidative stress and its influence on tumor growth. We have knocked down LATS1 in primary melanocytes and melanoma cells and found that its expression is crucial for melanin synthesis, ROS production, and oxidative stress response. We showed that LATS1 ablation significantly decreased the melanogenesis markers’ expression and melanin synthesis in melanocyte and melanoma cell lines. Moreover, silencing LATS1 resulted in enhanced oxidative stress. Reduced melanin content in LATS1 knocked down tumors was associated with increased tumor growth, pointing to melanin’s protective role in this process. The study demonstrated that LATS1 is highly engaged in melanogenesis and oxidative stress control and affects melanoma growth. Our results may find the implications in the diagnosis and treatment of pigmentation disorders, including melanoma.     

酵母提取物对多酚氧化酶及黑素瘤细胞的抑制作用

为了研究酵母提取物的美白作用,选取多酚氧化酶以及B16黑素瘤细胞株作为试验对象,验证酵母提取物对多酚氧化酶及黑素瘤细胞的抑制作用。结果表明酵母精华提取物对多酚氧化酶具有显著的抑制作用,并且可以抑制黑素瘤细胞中黑色素的形成,但对黑素瘤细胞的增殖没有明显抑制效果。     

Self-assembled biogenic melanin modulated surface chemistry of biopolymers-colloidal silica composite porous matrix for the recovery of uranium

A new composite porous matrix surface modulated by self-assembled melanin was developed and investigated for its affinity to bind uranium from an aqueous medium. The composite matrix was synthesized using biopolymers (i.e., agarose and alginate) and inorganic colloidal silica nanoparticles (AACS) by the process of cryotropic-gelation at subzero-temperature. Post-synthesis surface modification of AACS matrix with melanin (MAACS) was performed by green chemistry. The in situ sequestrial conversion of l -Dopa by the biocatalytic activity of tyrosinase enzyme allows the formation of melanin on the surface of AACS matrix. The functional moieties on the matrix display fast kinetics and high binding capacity with respect to uranium. MAACS matrix showed high porosity (~90%) with interconnected pores, high swelling kinetics and permeability. Other physicochemical properties of the matrix, such as thermal stability, storage modulus, and surface charge potential were found to be increased, while percent degradation decreased, which demonstrate improved properties of the matrix after impregnation of silica nanoparticles and surface functionalization with melanin. Thermodynamic parameters suggest that the binding of uranyl ions is passive and spontaneous. The concentrated recovery of uranium was achieved with reusability potential of adsorbent. These results suggest an environment friendly and safer method for the recovery of uranium. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46937.     

Development of kerosene fuel processing system for PEFC

Several liquid fuels have been applied for fuel processing systems for polymer electrolyte fuel cells (PEFCs). In these fuels, kerosene is very attractive for the stationary fuel cells because of its low price and superior infrastructure in Japan. Relatively high sulfur content and high carbon atom number of kerosene, however, bring a disadvantage in reforming activity. To overcome such a technical disadvantage, both desulfurization adsorbent and steam reforming catalyst were developed, and furthermore a fuel processing system for kerosene is evaluated by simulation.     

天然中草药美白祛斑化妆品

根据色斑的形成机理，采用相应的天然草本植物提取物淡化色斑。根据细胞内黑色素形成机理，选用适当抑制剂。减少黑色素的过量生成，防止皮肤表皮的继续黑化，提出美白与祛斑化妆品的合理配制方法。     

日本美白防晒化妆品

概述了日本护肤品市场以及美白防晒化妆品。介绍了日本的美白文化、美白防晒化妆品的历史及现状。论述了黑色素的生成机理及美白化妆品的作用。对日本的防紫外线商品市场进行了介绍。     

Targeted delivery of mitochondrial protectors prevents cardiolipin oxidation and cell degeneration following brain trauma or radiation injury

Reactive oxygen species (ROS) produced by injured cell powerhouses, mitochondria may lead to the development of heavy neuronal disorders of both chronic (Alzheimer disease, Parkinson disease, etc.) and acute brain injury followed by a secondary neuronal damage and death over time. Once a mitochondrion is injured, a phospholipid constituent of its inner membrane, cardiolipin (CL) undergoes externalization triggering a sequence of events which may lead to either natural elimination of injured mitochondria without the host cell injury or programmed host cell suicide, apoptosis. Mitochondria‐induced apoptosis is, among other, also responsible for radiation‐induced damage of radiosensitive organs like bone marrow and the small intestine. In order to prevent cell suicide, (per)oxygenation of externalized CL at the outer side of the inner mitochondrial membrane catalyzed by the cytochrome c/CL complex should be suppressed. Here some approaches that lead to the targeted suppression of ROS and inhibition of cyt c/CL complex (per)oxygenative activity within mitochondria are discussed, which provide the basis for the development of new anti‐apoptotic drugs defending the neuronal and other tissues from degeneration by ROS. The positive effects of these drugs were demonstrated in the laboratory animals developing secondary neuronal damage over time following traumatic brain injury or suffering from radiation‐induced disorders.     

4-Fluorobenzylpiperazine-Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase

Tyrosinase is a type-3 copper protein involved in the biosynthesis of melanin pigments; therefore, the inhibition of its enzymatic activity represents a promising strategy for the treatment of hyperpigmentation-related disorders. To address this point, we previously designed a class of 4-(4-fluorobenzyl)piperazin-1-yl-based compounds, which proved to be more active inhibitors against tyrosinase from mushroom Agaricus bisporus than the positive control kojic acid. Herein, we report the synthesis of further series of 4-(4-fluorobenzyl)piperazin-1-yl analogues bearing a (hetero)aromatic fragment as key feature to improve protein affinity. The newly synthesized compounds were assayed in vitro and proved to be potent inhibitors in the low-micromolar range. The active 2-thienyl and 2-furyl derivatives were selected for further modification to allow their binding mode to be analyzed by docking studies and to give satisfactory safety profiles.     

Investigation of the Anti-Melanogenic and Antioxidant Characteristics of Eucalyptus camaldulensis Flower Essential Oil and Determination of Its Chemical Composition

The effects of essential oil from Eucalyptus camaldulensis flowers oil on melanogenesis and the oil’s antioxidant characteristics were investigated. Assays of mushroom and cellular tyrosinase activities and melanin content of mouse melanoma cells were performed spectrophotometrically, and the expression of melanogenesis-related proteins was determined by Western blotting. The possible signaling pathways involved in essential oil-mediated depigmentation were also investigated using specific protein kinase inhibitors. The results revealed that E. camaldulensis flower essential oil effectively suppresses intracellular tyrosinase activity and decreases melanin amount in B16F10 mouse melanoma cells. The essential oil also exhibits antioxidant properties and effectively decreases intracellular reactive oxygen species (ROS) levels. The volatile chemical composition of the essential oil was analyzed with gas chromatography–mass spectrometry (GC/MS). The chemical constituents in the essential oil are predominately oxygenated monoterpenes (34.9%), followed by oxygenated sesquiterpenes (31.8%), monoterpene hydrocarbons (29.0%) and sesquiterpene hydrocarbons (4.3%). Our results indicated that E. camaldulensis flower essential oil inhibits melanogenesis through its antioxidant properties and by down-regulating both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways. The present study indicates that the essential oil has the potential to be developed into a skin care product.     

Prevention of melanin formation by yeast cerebroside in B16 mouse melanoma cells

The effects of plant and yeast cerebrosides on melanin formation were examined in B16 mouse melanoma cells. Addition of yeast cerebroside significantly reduced melanin content to the same level as that of arbutin in control cells, although there was no suppression by plant cerebrosides and bovine brain cerebroside up-regulated melanin formation. None of the bovine brain cerebrosides examined had any effect on tyrosinase activity, but yeast cerebroside reduced the contents of tyrosinase. The results of the present study clearly showed that melanin formation is regulated by several different cerebrosides via tyrosinase. In addition, the findings presented here suggest that cerebrosides containing a 9-methyl type sphingoid base, such as yeast cerebroside, may be useful as skincare products for suppressing melanin formation.     

Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms

The mechanisms by which the pigment melanin is transferred from melanocytes and processed within keratinocytes to achieve skin pigmentation remain ill-characterized. Nevertheless, several models have emerged in the past decades to explain the transfer process. Here, we review the proposed models for melanin transfer in the skin epidermis, the available evidence supporting each one, and the recent observations in favor of the exo/phagocytosis and shed vesicles models. In order to reconcile the transfer models, we propose that different mechanisms could co-exist to sustain skin pigmentation under different conditions. We also discuss the limited knowledge about melanin processing within keratinocytes. Finally, we pinpoint new questions that ought to be addressed to solve the long-lasting quest for the understanding of how basal skin pigmentation is controlled. This knowledge will allow the emergence of new strategies to treat pigmentary disorders that cause a significant socio-economic burden to patients and healthcare systems worldwide and could also have relevant cosmetic applications.     

Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders

As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle–brain, liver–brain and gut–brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise–brain communication and their benefits for physiology and brain function.     

Platelet Lysate Nebulization Protocol for the Treatment of COVID-19 and Its Sequels: Proof of Concept and Scientific Rationale

One of the most severe effects of coronavirus disease 2019 (COVID-19) is lung disorders such as acute respiratory distress syndrome. In the absence of effective treatments, it is necessary to search for new therapies and therapeutic targets. Platelets play a fundamental role in respiratory disorders resulting from viral infections, being the first line of defense against viruses and essential in maintaining lung function. The direct application of platelet lysate (PL) obtained from the platelet-rich plasma of healthy donors could help in the improvement of the patient due its anti-inflammatory, immunomodulatory, antifibrotic, and repairing effects. This work evaluates PL nebulization by analyzing its levels of growth factors and its biological activity on lung fibroblast cell cultures, besides describing a scientific basis for its use in this kind of pathology. The data of the work suggest that the molecular levels and biological activity of the PL are maintained after nebulization. Airway administration would allow acting directly on the lung tissue modulating inflammation and stimulating reparative processes on key structures such as the alveolocapillary barrier, improving the disease and sequels. The protocol developed in this work is a first step for the study of nebulized PL both in animal experimentation and in clinical trials.