Human Skin Pigmentation Research Articles

Oral administration of cysteine peptides attenuates UV-B-induced skin erythema and pigmentation in humans

The oral administration of antioxidants may suppress UV-B-induced skin damage. HITHION YH-15, the extract of Torula yeast (Cyberlindnera jadinii), is rich in cysteine-containing peptides such as reduced and oxidized glutathione (GSH and GSSG), γ-glutamylcysteine (γ-Glu-Cys), and cysteinylglycine (Cys-Gly). These four constituents are termed cysteine peptides. In this study, we investigated the protective effects of cysteine peptides against UV-B in a randomized, placebo-controlled, double-blind, parallel-group study. A total of 90 healthy males and females aged 30–59 years were enrolled and randomized into two groups of 45 individuals each (cysteine peptides (48 mg/day) and placebo). Changes in UV-B-induced erythema and pigmentation were compared between groups after 5 weeks of test food intake. The minimal erythema dose (MED) significantly increased (*p = 0.019) in the cysteine peptides group compared to that in the placebo group, indicating suppression of UV-B-induced erythema. ΔL* value significantly increased (***p < 0.0001) in the cysteine peptides group compared to that in the placebo, indicating pigmentation suppression. We demonstrated that oral administration of cysteine peptides suppresses UV-B-induced erythema and pigmentation through multiple mechanisms. Thus, cysteine peptides may find use as nutricosmetics for maintaining skin health and well-being.UMIN Clinical Trials Registry ID: UMIN 000050157.

An overview of benefits and risks of chronic melanocortin-1 receptor activation.

The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss-of-function MC1R variants suppress G protein-coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α-melanocortin-stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV-protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high-risk individuals.

The Potency of Adenostemma platyphyllum as Antimelanogenic Agent: In-vitro and In-silico Studies

Melanin is a crucial amino acid in determining human skin and hair pigmentation. Excessive melanin production can lead to hyperpigmentation and darkening of the skin. This study aims to assess the capability of Adenostemma platyphyllum as a tyrosinase enzyme inhibitor. It predicts its anti-melanogenic activity through molecular docking with proteins involved in the melanogenesis process. The in-vitro approach was conducted by determining the tyrosinase enzyme inhibition capacity, while the in-silico approach involved ligand binding to target proteins from melanogenesis pathways. The highest tyrosinase inhibition capacity was observed in the ethanol extract, with values of 9.74 Kojic Acid Equivalent (KAE)/g extract (L-tyrosine) and 17.91 (KAE)/g extract (L-DOPA). Molecular docking analysis showed that the binding of eriodictyol 7-O-sophoroside (ΔG = -9.7 kcal/mol) has the best energy affinity for the PKC-β protein, genistein (ΔG = -7.5 kcal/mol) for the tyrosinase-related protein-1 (TYRP1) protein, eriodictyol 7-O-sophoroside (ΔG = -10.2 kcal/mol) for the cGMP protein, vincosamide (ΔG = -7.2 kcal/mol) for the microphthalmia-associated transcription factor (MITF) protein, and dicaffeoylquinic acid (ΔG = -7.4 kcal/mol) for the β-catenin protein. Based on a comparison of in-vitro and in-silico studies, melanogenesis inhibition is more potent in the PKC-β and cGMP pathways than direct tyrosinase inhibition because they exhibit lower binding energy.

Human Skin Pigmentation: From a Biological Feature to a Social Determinant.

Skin pigmentation is the most variable human characteristic that can be observed and has been used throughout history to classify humans into distinct groups. Many factors influence skin colour, but the melanin pigment is considered the most important because its type and quantity can determine variations in pigmentation shades. The evolution of skin pigmentation started around 1.6-2 million years ago. As a result of migratory phenomena to places with less ultraviolet radiation (UVR) and other seasonal regimes, the selection of depigmented skin and different tanning capabilities occurred over time. Thus, genetic adaptation to new environmental conditions gradually led to changes in skin pigmentation. Despite the biological importance of pigmentation, variation in skin colour has led to social and health inequalities. Since Linnaeus, skin colour classifications have been used to describe different human groups, encouraging the misuse of a biological characteristic. This review examines the characterisation of pigmentation and its evolution through history and society. The unequal perception of pigmentation diversity has led to an incomplete state of dermatological training and issues in medical approach in dermatology. The consciousness of all these aspects increases the need to address and overcome dermatologic and social health disparities related to skin pigmentation.

Deconstructing Eurocentrism in skin pigmentation research via the incorporation of diverse populations and theoretical perspectives.

The evolution of skin pigmentation has been shaped by numerous biological and cultural shifts throughout human history. Vitamin D is considered a driver of depigmentation evolution in humans, given the deleterious health effects associated with vitamin D deficiency, which is often shaped by cultural factors. New advancements in genomics and epigenomics have opened the door to a deeper exploration of skin pigmentation evolution in both contemporary and ancient populations. Data from ancient Europeans has offered great context to the spread of depigmentation alleles via the evaluation of migration events and cultural shifts that occurred during the Neolithic. However, novel insights can further be gained via the inclusion of diverse ancient and contemporary populations. Here we present on how potential biases and limitations in skin pigmentation research can be overcome with the integration of interdisciplinary data that includes both cultural and biological elements, which have shaped the evolutionary history of skin pigmentation in humans.

Skin Pigmentation Types, Causes and Treatment-A Review.

Human skin pigmentation and melanin synthesis are incredibly variable, and are impacted by genetics, UV exposure, and some drugs. Patients' physical appearance, psychological health, and social functioning are all impacted by a sizable number of skin conditions that cause pigmentary abnormalities. Hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced, are the two major classifications of skin pigmentation. Albinism, melasma, vitiligo, Addison's disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosinase, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, 4 marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.

Toward a Synopsis of the Challenges Facing Mainstream Interpretations of Skin Pigmentation in Humans

When traditional or mainstream interpretations of skin pigmentation in humans were proposed, not much data was available about the anatomy of human skin in particular and pigment research in general. The most popular and influential thesis put forth to date to justify the evolution of skin pigmentation is the thesis that skin pigmentation grew out of a natural adaptation of Homo sapiens skin to scorching conditions of fiery heat faced with by Homo sapiens individuals in equatorial regions of Africa. It is thereby argued that peak UVR [ultraviolet rays] environments encountered in equatorial/savannah climate caused an eccrine gland production to offset the overheating of skin during the high physical activity of hunting exerted by Homo sapiens persons. However, with human anatomy increasingly becoming the object of scrutiny from various fronts of biology, newer insights have given rise to significant blind spots vis-&amp;agrave;-vis traditional explanations of black skin pigmentation. The present paper takes stock of the major challenges afflicting existing characterizations of human skin evolution. Paths for future research of skin/pigment are suggested. The paper aims to lay out a follow-up on and/or synopsis of recurrent challenges that the space of pigment research has accumulated over the years, giving way to long due synergies. In a world supersensitive to racial equality and dignity, the paper furnishes concerned researchers and policy makers with a much-needed contribution to inquiry into dark- and black-skinned peoples.

Optical Properties of Human Skin Phototypes and Their Correlation with Individual Angle Typology

Objective: This study aims to correlate human skin phototypes with complete optical characterization (absorption, scattering, effective attenuation, optical penetration, and albedo coefficients) based on individual typology angle (ITA) values and colorimetric parameters. Methods: A colorimeter was used to group 12, fresh, ex vivo human skin samples according to their phototype; the CIELAB color scale and ITA values were employed. An integrating sphere system and the inverse adding-doubling algorithm were applied during optical characterization, conducted from 500 to 1300 nm. Results: On the basis of ITA values and their classification, the skin samples were separated into six groups: two intermediates, two tan, and two brown. In the visible range, for lower ITA values (darker skins), the absorption and effective attenuation coefficient parameters increased, whereas the albedo and depth penetration parameters decreased. In the infrared region, all the phototypes had similar parameters. The scattering coefficient was similar for all the samples and did not change with ITA values. Conclusions: ITA analysis, a quantitative method, showed that the human skin tissue's optical properties and pigmentation colors were highly correlated.

Detection of Vitiligo Using Optical Sensor Based on 2-D Photonic Crystals

This structure proposes the creation of the optical biosensor that can be used to detect vitiligo caused to pigment loss. For accomplishing this, a pair of 2-D photonic crystal structures, such as the K3 and K7 resonators, are examined. The study of both resonator structures is succeeded using (FDTD) Finite Difference Time Domain. The Lumerical simulation tool is used to model these structures in the Finite Difference Time Domain (FDTD). The subsequent optical properties of different pigmentation in human skin are investigated, and the refractive indexes information are entered into Lumerical (FDTD) to find variations in the refractive indexes of several pigments that produce vitiligo.

The influence of copper ions on the transport and relaxation properties of hydrated eumelanin.

Eumelanin, the human skin pigment, is a poly-indolequinone material possessing a unique combination of physical and chemical properties. For numerous applications, the conductivity of eumelanin is of paramount importance. However, its hydration dependent conductivity is not well studied using transport-relaxation methods. Furthermore, there is no such work taking into account the simultaneous control of humidity as well as metal ion concentration. Here we present the first such study of the transport and relaxation characteristics of synthetic eumelanin doped with various Cu ion concentrations while controlling the humidity with a frequency range of 10-3 Hz-1 MHz. We found that Cu ions do not cause the appearance of additional relaxation processes, but partially slow down those present in neat eumelanin. In addition, considering previously published work, the key relaxation process observed in doped and undoped materials is associated with the moisture-induced synthesis of uncharged semiquinones and a corresponding increase in the overall aromaticity of the material.

An exclusive review of melatonin effects on mammalian melanocytes and melanoma.

Melatonin influences mammalian coat colour and hair follicle pigmentation and also weakly alters the electrical stimulation of retinal cells in the eyes. A direct melanocytic response to melatonin is still uncertain in mammals and human skin pigmentation. Melatonin acts as a free radical scavenger and thus inhibits the initiation of cancer cell growth. Treatment of melanoma sees perspective features in the administration of melatonin along with known chemotherapeutic molecules to improve the efficacy of conventional cytotoxic agents. Being richly supplied with a variety of receptors, melanocytes and melanoma cells can be used as in vitro test models for pharmacological applications of known and novel drugs.

Kinetics of Tyrosinase Inhibition, Antioxidant Activity, Total Flavonoid Content and Analysis of Averrhoa bilimbi L. Extracts and its Fruit Vinegar Using FTIR and Multivariate Methods

Melanin is a natural substance responsible for human skin pigmentation. Tyrosinase is known as a key enzyme involved in melanin production; therefore, hyperactivity of this enzyme leads to hyperpigmentation in human. In current study, leaves and fruits of Averrhoa bilimbi L. were extracted with ethanol and water solvents, and its fruit vinegar was produced by fermenting fresh fruits with sugar at room temperature for 10 days. The leaf and aqueous extracts of A. bilimbi L. and its fruit vinegar were investigated for tyrosinase inhibitory activity using L-DOPA as substrates, antioxidant activity using 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation decolorization assay and total flavonoid content (TFC) using aluminium chloride colorimetric method. Moreover, kinetic study of anti-tyrosinase activity of A. bilimbi extracts and its fruit vinegar, including Fourier transform infrared (FTIR) spectra and principal component analysis (PCA) were carried out. The result indicated ethanol extracts from A. bilimbi fruits and leaves showed the highest TFC and anti-tyrosinase activity, whereas aqueous extracts of its fruits and leaves showed the highest radical scavenging activity. Interestingly, the result revealed the existence of TFC, radical scavenging activity and anti-tyrosinase activity in the vinegar sample. The anti-tyrosinase potential of the fruit and leaf ethanol extracts of A. bilimbi was identified as an uncompetitive inhibitor (Km= 0.54 and 0.51 µM, Vmax= 0.0173 and 0.0146 O.D.450/min, respectively). Positive correlation was significantly found between radical scavenging activity and TFC, between anti-tyrosinase activity and TFC, between FTIR data and TFC, and between FTIR data and anti-tyrosinase activity, (r = 0.83, 0.56, 0.66, 0.75; p-value &lt; 0.05, respectively). Therefore, the extracts and fruit vinegar of A. bilimbi L. could be considered as natural source of an anti-tyrosinase compounds for cosmetics and healthy foods. HIGHLIGHTS The ethanol extracts and fruit vinegar showed high flavonoid content, antioxidant activity and anti-tyrosinase activity The anti-tryrosinase potential was identified as an uncompetitive inhibitor Positive correlation was significantly found between chemical and biological data FTIR, PCA and cluster analysis showed differentiation between extracts and its fruit vinegar GRAPHICAL ABSTRACT

Advances in Pigmentation Management: A Multipronged Approach.

Key cellular players regulating human skin pigmentation include melanocytes in the epidermis that synthesize melanin, neighboring keratinocytes that receive and distribute melanin in the upper layers, and fibroblasts in the dermis that affect overlying melanocytes and keratinocytes. In addition, endocrine factors from the blood supply (endothelial cells) and inflammation-related factors play a role. Thus, new strategies for affecting pigmentation need to consider these multiple cell lines to adequately cover various causes and disease processes associated with hyperpigmentation. Pathophysiologic mechanisms and cellular pathways involved in melanogenesis were thoroughly reviewed with particular emphasis on the cellular interplay involved in the process. A complex system of interlinking and independent pathways was defined and described demonstrating differing pathways for altered pigmentary disorders - melasma associated with endothelial cell interactions; post inflammatory hyperpigmentation associated with keratinocyte inflammatory mediators (PGE2 in particular); and photodamage involving all 4 cell types. In vitro validation studies were then undertaken to define differing cell group gene expression profiles with selected peptides and other active agents. Melanocytic production of pigment was then tested with these agents to identify key potential players capable of limiting pigmentation. Hexapeptide-12 and lactoferrin (melanocytes), Hexapeptide-11 (in keratinocytes), and phosphatidylserine (endothelial cells) were identified as major inhibitors of melanogenesis based on their gene expression profiles. This was confirmed by secondary melanin production tests performed on melanocytic lines. Additional active agents were also identified as inhibitors of melanocytic production of melanin, and together, these constituents formed the basis for a novel formulation for use in pigmentary disorders. A comprehensive scientific narrative of the various facets relating to pigmentation has been presented including differing pathways affecting varied cell lines that effect pigment production. Based on this concept, actives were tested using gene expression studies as well as in vitro melanogenic model testing in different cell lines. Using this novel multi-faceted approach, we have selected and validated a series of active agents to be used in a formulation targeting the complex problem of hyperpigmentation. J Drugs Dermatol. 2022;21(11):1206-1220. doi:10.36849/JDD.7013.

Endogenous DOPA inhibits melanoma through suppression of CHRM1 signaling.

Melanoma risk is 30 times higher in people with lightly pigmented skin versus darkly pigmented skin. Using primary human melanocytes representing the full human skin pigment continuum and preclinical melanoma models, we show that cell-intrinsic differences between dark and light melanocytes regulate melanocyte proliferative capacity and susceptibility to malignant transformation, independent of melanin and ultraviolet exposure. These differences result from dihydroxyphenylalanine (DOPA), a melanin precursor synthesized at higher levels in melanocytes from darkly pigmented skin. We used both high-throughput pharmacologic and genetic in vivo CRISPR screens to determine that DOPA limits melanocyte and melanoma cell proliferation by inhibiting the muscarinic acetylcholine receptor M1 (CHRM1) signaling. Pharmacologic CHRM1 antagonism in melanoma leads to depletion of c-Myc and FOXM1, both of which are proliferation drivers associated with aggressive melanoma. In preclinical mouse melanoma models, pharmacologic inhibition of CHRM1 or FOXM1 inhibited tumor growth. CHRM1 and FOXM1 may be new therapeutic targets for melanoma.

In vivo multiphoton multiparametric 3D quantification of human skin aging on forearm and face

Quantifying skin aging changes and characterizing its 3D structure and function in a non-invasive way is still a challenging area of research, constantly evolving with the development of imaging methods and image analysis tools. In vivo multiphoton imaging offers means to assess skin constituents in 3D, however prior skin aging studies mostly focused on 2D analyses of dermal fibers through their signals’ intensities or densities. In this work, we designed and implemented multiphoton multiparametric 3D quantification tools for in vivo human skin pigmentation and aging characterization. We first demonstrated that despite the limited field of view of the technic, investigation of 2 regions of interest (ROIs) per zone per volunteer is a good compromise in assessing 3D skin constituents in both epidermis and superficial dermis. We then characterized skin aging on different UV exposed areas—ventral and dorsal forearms, face. The three major facts of aging that are epidermal atrophy, the dermal–epidermal junction (DEJ) flattening and dermal elastosis can be non-invasively quantified and compared. Epidermal morphological changes occur late and were only objectified between extreme age groups. Melanin accumulation in suprabasal layers with age and chronic exposure on ventral and dorsal forearms is less known and appears earlier. Superficial dermal aging changes are mainly elastin density increase, with no obvious change in collagen density, reflected by SHGto2PEF ratio and SAAID index decrease and ImbrN index increase on all skin areas. Analysis of the z-dermal distribution of these parameters highlighted the 2nd 20 µm thickness normalized dermal sub-layer, that follows the DEJ shape, as exhibiting the highest aging differences. Moreover, the 3D ImbrN index allows refining the share of photoaging in global aging on face and the 3D SAAID index on forearm, which elastin or fibrillar collagens densities alone do not allow. Photoaging of the temple area evolves as a function of chronic exposure with a more pronounced increase in elastin density, also structurally modified from thin and straight elastic fibers in young volunteers to dense and compact pattern in older ones. More generally, multiphoton multiparametric 3D skin quantification offers rich spatial information of interest in assessing normal human skin condition and its pathological, external environment or product induced changes.

BCI-215, a Dual-Specificity Phosphatase Inhibitor, Reduces UVB-Induced Pigmentation in Human Skin by Activating Mitogen-Activated Protein Kinase Pathways.

Background: The dysregulation of melanin production causes skin-disfiguring ultraviolet (UV)-associated hyperpigmented spots. Previously, we found that the activation of c-Jun N-terminal kinase (JNK), a mitogen-activated protein kinase (MAPK), inhibited melanogenesis. Methods: We selected BCI-215 as it may modify MAPK expression via a known function of a dual-specificity phosphatase (DUSP) 1/6 inhibitor. B16F10 melanoma cells, Mel-ab cells, human melanocytes, and a coculture were used to assess the anti-melanogenic activity of BCI-215. The molecular mechanisms were deciphered by assaying the melanin content and cellular tyrosinase activity via immunoblotting and RT-PCR. Results: BCI-215 was found to suppress basal and cAMP-stimulated melanin production and cellular tyrosinase activity in vitro through the downregulation of microphthalmia-associated transcription factor (MITF) protein and its downstream enzymes. The reduction in MITF expression caused by BCI-215 was found to be due to all three types of MAPK activation, including extracellular signal-regulated kinase (ERK), JNK, and p38. The degree of activation was greater in ERK. A phosphorylation of the β-catenin pathway was also demonstrated. The melanin index, expression of MITF, and downstream enzymes were well-reduced in UVB-irradiated ex vivo human skin by BCI-215. Conclusions: As BCI-215 potently inhibits UV-stimulated melanogenesis, small molecules of DUSP-related signaling modulators may provide therapeutic benefits against pigmentation disorders.

653 Endogenous DOPA inhibits melanoma through suppression of CHRM1 signaling

Melanoma risk is 30 times higher in people with lightly pigmented skin compared to those with darkly pigmented skin. Here we show that this difference results from more than melanin pigment and its associated ultraviolet radiation (UVR) shielding effect. Using primary human melanocytes representing the full human skin pigment continuum and several preclinical melanoma models, we show that cell-intrinsic differences between dark and light melanocytes regulate melanocyte proliferative capacity, overall cellular differentiation state, and susceptibility to malignant transformation, independently of melanin and UV exposure. We determined that these differences result from dihydroxyphenylalanine (DOPA), a melanin precursor synthesized at higher levels in melanocytes from dark skin. Although DOPA was not previously known to have specific signaling activity, we used both high throughput pharmacologic and genetic in vivo CRISPR screens to determine that DOPA limits melanocyte and melanoma cell proliferation by inhibiting the muscarinic acetylcholine receptor M1 (CHRM1), a G Protein-Coupled Receptor (GPCR) not previously known to interact with DOPA, nor to affect melanoma pathobiology. Pharmacologic CHRM1 antagonism in melanoma leads to depletion of c-Myc and FOXM1, both of which are proliferation drivers associated with aggressive melanoma. In preclinical mouse melanoma models using both immune deficient and syngeneic immune competent mice, pharmacologic inhibition of CHRM1 or FOXM1 inhibited tumor growth. CHRM1 and FOXM1 may be new therapeutic targets for melanoma.

The evolution of human skin pigmentation: A changing medley of vitamins, genetic variability, and UV radiation during human expansion.

This review examines putative, yet likely critical evolutionary pressures contributing to human skin pigmentation and subsequently, depigmentation phenotypes. To achieve this, it provides a synthesis of ideas that frame contemporary thinking, without limiting the narrative to pigmentation genes alone. It examines how geography and hence the quality and quantity of UV exposure, pigmentation genes, diet-related genes, vitamins, anti-oxidant nutrients, and cultural practices intersect and interact to facilitate the evolution of human skin color. The article has a strong focus on the vitamin D-folate evolutionary model, with updates on the latest biophysical research findings to support this paradigm. This model is examined within a broad canvas that takes human expansion out of Africa and genetic architecture into account. A thorough discourse on the biology of melanization is provided (includes relationship to BH4 and DNA damage repair), with the relevance of this to the UV sensitivity of folate and UV photosynthesis of vitamin D explained in detail, including the relevance of these vitamins to reproductive success. It explores whether we might be able to predict vitamin-related gene polymorphisms that pivot metabolism to the prevailing UVR exposome within the vitamin D-folate evolutionary hypothesis context. This is discussed in terms of a primary adaptive phenotype (pigmentation/depigmentation), a secondary adaptive phenotype (flexible metabolic phenotype based on vitamin-related gene polymorphism profile), and a tertiary adaptive strategy (dietary anti-oxidants to support the secondary adaptive phenotype). Finally, alternative evolutionary models for pigmentation are discussed, as are challenges to future research in this area.

Synthesis and Tyrosinase Inhibitory Activity of (E)-5-Benzyl-7- (3-Bromobenzylidene)-3-(3-Bromophenyl)-2-Phenyl-3,3a, 4,5,6,7-Hexahydro-2H-Pyrazolo[4,3-c]Pyridine

The tyrosinase enzyme plays an essential role in the pigmentation of human skin, fruits, and vegetables. It has been tied with several human skin diseases and post-harvest problems. Hence, the tyrosinase enzyme becomes an excellent therapeutic target to overcome these issues. This study aimed to screen tyrosinase inhibitors by synthesizing halogen-substituted pyrazolopyridine derivatives. The pyrazolopyridine compound was obtained through two stages of synthesis. First, the intermediate compound, a derivative of 3,5-bis(arylidene)-4-piperidone, was synthesized through the Cleisen-Schmidt condensation reaction of 4-piperidone and benzaldehyde derivatives. Furthermore, the intermediate compound was reacted with phenylhydrazine through a cyclocondensation reaction to produce the titled compound with an 11% yield. The chemical structure of the target compound was identified through the interpretation of UV, FTIR, NMR, and HRMS spectra. Then an in vitro assay was conducted on the tyrosinase enzyme of the fungus Agaricus bisporus by detecting the presence of dopachrome at a wavelength of 492 nm. As a result, the in vitro assay showed that the titled compound had a weak inhibitory activity, and the IC50 value was &gt; 500 µM. Thus, the synthesized compound is considered inactive.

In vivo imaging with a fast large-area multiphoton exoscope (FLAME) captures the melanin distribution heterogeneity in human skin

Melanin plays a significant role in the regulation of epidermal homeostasis and photoprotection of human skin. The assessment of its epidermal distribution and overall content is of great interest due to its involvement in a wide range of physiological and pathological skin processes. Among several spectroscopic and optical imaging methods that have been reported for non-invasive quantification of melanin in human skin, the approach based on the detection of two-photon excited fluorescence lifetime distinguishes itself by enabling selective detection of melanin with sub-cellular resolution, thus facilitating its quantification while also resolving its depth-profile. A key limitation of prior studies on the melanin assessment based on this approach is their inability to account for the skin heterogeneity due to the reduced field of view of the images, which results in high dispersion of the measurement values. Pigmentation in both normal and pathological human skin is highly heterogeneous and its macroscopic quantification is critical for reliable measurements of the epidermal melanin distribution and for capturing melanin-related sensitive dynamic changes as a response to treatment. In this work, we employ a fast large-area multiphoton exoscope (FLAME), recently developed by our group for clinical skin imaging, that has the ability to evaluate the 3D distribution of epidermal melanin content in vivo macroscopically (millimeter scale) with microscopic resolution (sub-micron) and rapid acquisition rates (minutes). We demonstrate significant enhancement in the reliability of the melanin density and distribution measurements across Fitzpatrick skin types I to V by capturing the intra-subject pigmentation heterogeneity enabled by the large volumetric sampling. We also demonstrate the potential of this approach to provide consistent measurement results when imaging the same skin area at different times. These advances are critical for clinical and research applications related to monitoring pigment modulation as a response to therapies against pigmentary skin disorders, skin aging, as well as skin cancers.