Characterization of adults concerning the use of a hypothetical mHealth application addressing stress-overeating: an online survey.

BACKGROUND: About 40% of people respond to stress by consuming more unhealthy foods. This behavior is associated with increased energy intake and the risk of obesity. As mobile health (mHealth) applications (apps) have been shown to be an easy-to-use intervention tool, the characterization of potential app users is necessary to develop target group-specific apps and to increase adherence rates. METHODS: This cross-sectional online survey was conducted in the spring of 2021 in Germany. Sociodemographic data and data on personality (Big Five Inventory, BFI-10), stress-eating (Salzburg Stress Eating Scale, SSES), and technology behavior (Personal Innovativeness in the Domain of Information Technology, PIIT; Technology Acceptance Model 3, TAM 3) were collected. RESULTS: The analysis included 1228 participants (80.6% female, mean age: 31.4 ± 12.8 years, mean body mass index (BMI): 23.4 ± 4.3 kg/m2). Based on the TAM score, 33.3% (409/1228) of the participants had a high intention to use a hypothetical mHealth app to avoid stress-overeating. These persons are characterized by a higher BMI (24.02 ± 4.47 kg/m2, p < 0.001), by being stress-overeaters (217/409, 53.1%), by the personality trait "neuroticism" (p < 0.001), by having specific eating reasons (all p < 0.01), and by showing a higher willingness to adopt new technologies (p < 0.001). CONCLUSION: This study suggests that individuals who are prone to stress-overeating are highly interested in adopting an mHealth app as support. Participants with a high intention to use an mHealth app seem to have a general affinity towards new technology (PIIT) and appear to be more insecure with conflicting motives regarding their diet. TRIAL REGISTRATION: This survey was registered in the German Clinical Trials Register (Registration number: DRKS00023984).

Ultraviolet Radiation-Induced Mitochondrial Disturbances Are Attenuated by Metabolites of Melatonin in Human Epidermal Keratinocytes.

Melatonin (N-acetyl-5-methoxytryptamine) is recognized as an effective antioxidant produced by the pineal gland, brain and peripheral organs, which also has anti-inflammatory, immunomodulatory, and anti-tumour capacities. Melatonin has been reported as a substance that counteracts ultraviolet radiation B (UVB)-induced intracellular disturbances. Nevertheless, the mechanistic actions of related molecules including its kynurenic derivatives (N1-acetyl-N2-formyl-5-methoxykynurenine (AFMK)), its indolic derivatives (6-hydroxymelatonin (6(OH)MEL) and 5-methoxytryptamine (5-MT)) and its precursor N-acetylserotonin (NAS) are only poorly understood. Herein, we treated human epidermal keratinocytes with UVB and assessed the protective effect of the studied substances in terms of the maintenance of mitochondrial function or their radical scavenging capacity. Our results show that UVB caused the significant elevation of catalase (CAT) and superoxide dismutase (Mn-SOD), the dissipation of mitochondrial transmembrane potential (mtΔΨ), a reduction in ATP synthesis, and the enhanced release of cytochrome c into cytosol, leading subsequently to UVB-mediated activation of the caspases and apoptosis (appearance of sub-G1 population). Our findings, combined with data reported so far, indicate the counteracting and beneficial actions of melatonin and its molecular derivatives against these deleterious changes within mitochondria. Therefore, they define a path to the development of novel strategies delaying mitochondrial aging and promoting the well-being of human skin.

Melatonin: A Potential Regulator of DNA Methylation.

The pineal gland-derived indoleamine hormone, melatonin, regulates multiple cellular processes, ranging from chronobiology, proliferation, apoptosis, and oxidative damage to pigmentation, immune regulation, and mitochondrial metabolism. While melatonin is best known as a master regulator of the circadian rhythm, previous studies also have revealed connections between circadian cycle disruption and genomic instability, including epigenetic changes in the pattern of DNA methylation. For example, melatonin secretion is associated with differential circadian gene methylation in night shift workers and the regulation of genomic methylation during embryonic development, and there is accumulating evidence that melatonin can modify DNA methylation. Since the latter one impacts cancer initiation, and also, non-malignant diseases development, and that targeting DNA methylation has become a novel intervention target in clinical therapy, this review discusses the potential role of melatonin as an under-investigated candidate epigenetic regulator, namely by modulating DNA methylation via changes in mRNA and the protein expression of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins. Furthermore, since melatonin may impact changes in the DNA methylation pattern, the authors of the review suggest its possible use in combination therapy with epigenetic drugs as a new anticancer strategy.

PTPN11 Mosaicism Causes a Spectrum of Pigmentary and Vascular Neurocutaneous Disorders and Predisposes to Melanoma.

Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic group and high-depth next-generation sequencing of affected tissues, we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis pigmentovascularis type III or spilorosea. Within an individual, the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to show that the same variants can cause either the pigmentary or vascular phenotypes alone, and drive melanoma development within pigmentary lesions. Protein structure modeling highlights that although variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modeling of the missense variants confirms downstream MAPK pathway overactivation and widespread disruption of human endothelial cell angiogenesis. Importantly, patients with PTPN11 mosaicism theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of nevus spilus and capillary malformation syndromes, paving the way for better clinical management.

Protective Role of Melatonin and Its Metabolites in Skin Aging.

The skin, being the largest organ in the human body, is exposed to the environment and suffers from both intrinsic and extrinsic aging factors. The skin aging process is characterized by several clinical features such as wrinkling, loss of elasticity, and rough-textured appearance. This complex process is accompanied with phenotypic and functional changes in cutaneous and immune cells, as well as structural and functional disturbances in extracellular matrix components such as collagens and elastin. Because skin health is considered one of the principal factors representing overall "well-being" and the perception of "health" in humans, several anti-aging strategies have recently been developed. Thus, while the fundamental mechanisms regarding skin aging are known, new substances should be considered for introduction into dermatological treatments. Herein, we describe melatonin and its metabolites as potential "aging neutralizers". Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. It regulates circadian rhythmicity and also exerts anti-oxidative, anti-inflammatory, immunomodulatory, and anti-tumor capacities. The intention of this review is to summarize changes within skin aging, research advances on the molecular mechanisms leading to these changes, and the impact of the melatoninergic anti-oxidative system controlled by melatonin and its metabolites, targeting the prevention or reversal of skin aging.

Stress-induced hyperphagia: empirical characterization of stress-overeaters.

BACKGROUND: Stressful situations can have an impact on an individual's eating behavior. People vulnerable to the influence of stress tend to change the quantity and quality of their food intake. Variables such as sex and body mass index (BMI) seem to be related to this stress-eating behavior, but it is rather unclear what factors account to the parameters associated with stress-eating behavior. The aim of this survey was to identify further characteristics of adults in Germany related to stress-overeating, focusing on stress perception, coping, eating motives and comfort foods as well as personality types. METHODS: This online survey was performed throughout Germany and comprised a 38-item pre-tested questionnaire. Stress-induced overeating was classified based on the Salzburg Stress Eating Scale (SSES). Moreover, validated questionnaires were used to identify additional characteristics of stress eaters. Participants were recruited using a convenience sampling approach, and data were collected between January and April 2021. RESULTS: The overall sample consisted of 1222 participants (female 80.8%, aged 31.5±12.8). 42.1% of participants were identified as stress-overeaters. Among the remaining group, 78.9% stated to eat less, 21.1% to eat equally when stressed. Female participants had a higher mean SSES score compared to male participants. The BMI was positively correlated to SSES, r(1220)=0.28, p>0.005. 'Agreeableness' (BigFive) was found to be a negative predictor of stress-overeating. The most pronounced difference in eating motives (The Eating Motivation Survey, TEMS) was found for 'Affect Regulation' and 'Weight Control'. CONCLUSIONS: The results indicate that stress-overeating affects a large proportion of the surveyed population. BMI, personality and eating motives additionally characterize stress-overeaters and may contribute to develop new approaches to address unhealthy stress-related eating patterns.

Alemtuzumab-induced Alopecia areata - a case report and systematic literature review of adverse events associated with Alemtuzumab.

Alemtuzumab is currently approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS). Despite the efficacy of this therapy several side effects in the skin have been noted during or after infusion including vitiligo, alopecia areata, malignant skin tumors and infections. Awareness of these effects and their treatment is of essential interdisciplinary importance. This minireview provides an overview of the dermatological side effects described in the current literature. We also suggest pathomechanisms underlying these phenomena. To introduce this review, we present the case of a woman with RRMS who developed severe alopecia areata for the first time on alemtuzumab.

[Melanocortin peptides : Fundamentals, translational research, clinical dermatology, and future perspectives]. / Melanokortinpeptide : Grundlagen, translationale Forschung, klinische Dermatologie und Zukunftsperspektiven.

Melanocortins are peptides that share a common central pharmacophor. Melanin pigmentation of interfollicular epidermis and hair via MC1R remains the key physiologic function of the naturally occurring melanocortin peptides in skin. Moreover, the melanocortins are crucially involved in the ultraviolet light-induced tanning response. Under pathophysiologic conditions, melanocortin peptides induce cutaneous hyperpigmentation, likewise via the MC1R axis, e.g. in patients with Addison's disease, ectopic precursor pro-opiomelanocortin (POMC) syndrome and in those with abnormally elevated melanocortin blood levels. Translational research on α­MSH (melanocyte-stimulating hormones) and their antagonists has further revealed a variety of other biological activities beyond pigmentation. They include cytoprotection, antioxidative effects, regulation of collagen metabolism and fibrosis, sebum production, and cutaneous wound healing. These findings have also promoted the development of novel therapies in clinical dermatology including the exploitation of afamelanotide. In 2015, this agent became the first in-class synthetic α­MSH analogue to be approved in dermatology for the treatment of erythropoetic protoporphyria. In addition to afamelanotide, setmelanotide has recently emerged as a highly selective MC4R agonist useful for the treatment of distinct forms of genetically determined obesity, e.g., POMC deficiency. Future perspectives in dermatology reside in treatment of other difficult-to-treat skin diseases with α­MSH analogues, either with topical or systemic formulations. Moreover, synthetic melanocortin peptide derivatives lacking the central pharmacophor but with maintained anti-inflammatory effects could become a promising strategy for the design of new therapies in dermatology.

Can melatonin and its metabolites boost the efficacy of targeted therapy in patients with advanced melanoma?

Despite groundbreaking new treatments such as checkpoint inhibition and targeted therapy, the overall response and survival rates are limited in patients with metastatic melanoma. Here, we hypothesize that melatonin and its metabolites could be promising boosters of the efficacy of BRAF/MEK inhibitors in patients with advanced melanoma. Melatonin, a well-known endogenous synchronizer of the circadian biorhythm has a variety of promising effects for melanoma biology. It regulates proliferation, apoptosis and oxidative phosphorylation via melatonin receptors, and receptor-independent pathways due to its lipophilicity. By means of interfering with the above cellular pathways, melatonin and related compounds may alter the cAMP-PKA-MITF axis, modulate tumor cell metabolism, affect MAPK signalling pathway thereby enhancing the suppressive effect of BRAF/MEK inhibitors on melanoma cell growth, and survival. Such findings could fuel preclinical studies and clinical studies where melatonin or its metabolites are combined with targeted therapy to better treat patients with metastatic melanoma.

Paired Basic Amino Acid-cleaving Enzyme 4 (PCSK6): An Emerging New Target Molecule in Human Melanoma.

Although recent therapeutic developments raise hope, melanoma remains a devastating disease with a need for new treatment targets. In other tumours prohormone convertases have been shown to be pro-tumourigenic as they are involved in processing preforms of matrix-metalloproteinases, growth factors and adhesion molecules. The aim of this study was to look for new treatment options for melanoma, by investigating the role of the prohormone convertase Paired basic Amino acid-Cleaving Enzyme 4 (PACE4/PCSK6) in melanoma cell lines and human melanoma tissue. PACE4-transfected A375 melanoma cells displayed significantly increased proliferation, MMP-2 production, gelatinase activity and migratory capacity in vitro compared with sham-transfected cells. In vivo, elevated PACE4 expression resulted in significantly increased tumour growth on immunodeficient mice. In the majority of 45 human primary melanomas and melanoma metastases ex vivo PACE4 immunoreactivity was detectable, while it was absent in in situ melanomas. These results indicate PACE4 as a regulator of melanoma cell aggressiveness.

The α7 Nicotinic Acetylcholine Receptor: A Promising Target for the Treatment of Fibrotic Skin Disorders.

Targeting neuroendocrine receptors can be considered as another interesting approach to treating fibrotic disorders. Previously, we could demonstrate that tropisetron, a classical serotonin receptor blocker, can modulate collagen synthesis and acts in vitro through the α7 nicotinic acetylcholine receptor (α7nAchR). Here, we used a pharmacologic approach with specific α7nAchR agonists to validate this hypothesis. PHA-543613, an α7nAchR-specific agonist, not only prevented but also reversed established skin fibrosis of mice injected with bleomycin. Interestingly, agonistic stimulation of α7nAchR also attenuated experimental skin fibrosis in the non-inflammation driven adenovirus coding for TGFß receptor Iact mouse model, indicating fibroblast-mediated and not only anti-inflammatory effects of such agents. The fibroblast-mediated effects were confirmed in vitro using human dermal fibroblasts, in which the α7nAchR-specific agonists strongly reduced the impact of TGFß1-mediated expression on collagen and myofibroblast marker expression. These actions were linked to modulation of the redox-sensitive transcription factor JunB and impairment of the mitochondrial respiratory system. Our results indicate that pharmacologic stimulation of the α7nAchR could be a promising target for treatment of patients with skin fibrotic diseases. Moreover, our results suggest a mechanistic axis of collagen synthesis regulation through the mitochondrial respiratory system.

Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT-1 melanoma cells.

Melanogenesis is a key parameter of differentiation in melanocytes and melanoma cells; therefore, search for factors regulating this pathway are strongly desired. Herein, we investigated the effects of melatonin, a ubiquitous physiological mediator that is found throughout animals and plants. In mammals, the pineal gland secretes this indoleamine into the blood circulation to exert an extensive repertoire of biological activities. Our in vitro assessment indicates an oncostatic capacity of melatonin in time-dependent manner (24, 48, 72 hours) in highly pigmented MNT-1 melanoma cells. The similar pattern of regulation regarding cell viability was observed in amelanotic Sk-Mel-28 cells. Subsequently, MNT-1 cells were tested for the first time for evaluation of melanin/melatonin interaction. Thus primary, electron paramagnetic resonance (EPR) spectroscopy demonstrated that melatonin reduced melanin content. Artificially induced disturbances of melanogenesis by selected inhibitors (N-phenylthiourea or kojic acid) were slightly antagonized by melatonin. Additionally, analysis using transmission electron microscopy has shown that melatonin, particularly at higher dose of 10-3  mol/L, triggered the appearance of premelanosomes (stage I-II of melanosome) and MNT-1 cells synthesize de novo endogenous melatonin shown by LC-MS. In conclusion, these studies show a melanogenic-like function of melatonin suggesting it as an advantageous agent for treatment of pigmentary disorders.

Transepidermal UV radiation of scalp skin ex vivo induces hair follicle damage that is alleviated by the topical treatment with caffeine.

OBJECTIVES: Although the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine. METHODS: Human scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm2 UVA (340-440 nm) + 20 mJ/cm2 UVB (290-320 nm) (low dose) or 50 J/cm2 UVA + 50 mJ/cm2 UVB (high dose) and organ-cultured under serum-free conditions for 1 or 3 days. 0.1% caffeine (5.15 mmol/L) was topically applied for 3 days prior to UV exposure with 40 J/cm2 UVA + 40 mJ/cm2 UVB and for 3 days after UVR. The effects on various toxicity and vitality read-out parameters were measured in defined skin and HF compartments. RESULTS: Consistent with previous results, transepidermal UVR exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low UVA+UVB doses also induced oxidative DNA damage and cytotoxicity in human HFs. In addition, it decreased proliferation and promoted apoptosis of HF outer root sheath (ORS) and hair matrix (HM) keratinocytes, stimulated catagen development, differentially regulated the expression of HF growth factors, and induced perifollicular mast cell degranulation. UVR-mediated HF damage was more severe after irradiation with high UVR dose and reached also proximal HF compartments. The topical application of 0.1% caffeine did not induce skin or HF cytotoxicity and stimulated the expression of IGF-1 in the proximal HF ORS. However, it promoted keratinocyte apoptosis in selected HF compartments. Moreover, caffeine provided protection towards UVR-mediated HF cytotoxicity and dystrophy, keratinocyte apoptosis, and tendential up-regulation of the catagen-promoting growth factor. CONCLUSION: Our study highlights the clinical relevance of our scalp UV irradiation ex vivo assay and provides the first evidence that transepidermal UV radiation negatively affects important human HF functions. This suggests that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as HF photoprotectants into sun-protective cosmeceutical and nutraceutical formulations.

OBJECTIFS: Alors que l'effet de rayons ultraviolets (RUV) sur la peau humaine a été largement étudié, on sait très peu de choses de l'impact des UV sur l'homéostasie du follicule pileux (FP). Ici, nous avons étudié l'effet du spectre des RUV solaires qui atteignent la surface de la peau humaine sur la biologie du FP, et si tout effet nocif peut être atténué par de la caféine, un ingrédient cosmétique et neutraceutique largement utilisé. MÉTHODES: Une peau de cuir chevelu humain avec ses FP terminaux a été irradiée ex vivo via l'épiderme soit par 10 J/cm2 d'UVA (340-440 nm) + 20 mJ/cm2 d'UVB (290-320 nm) (dose faible) soit par 50 J/cm2 d'UVA + 50 mJ/cm2 d'UVB (dose élevée) et placée en culture sans sérum pendant 1 ou 3 jours. 0,1% (5,15 mM) de caféine a été appliquée par voie topique pendant 3 jours avant l'exposition aux UV à raison de 40 J/cm2 d'UVA + 40 mJ/cm2 UVB et pendant 3 jours après l'exposition aux RUV. Les effets sur divers paramètres de toxicité et de vitalité ont été mesurés au niveau de compartiments définis de la peau et des FP. RÉSULTATS: Cohérent avec les résultats précédents, les RUV transépidermique ont exercé une cytotoxicité au niveau de la peau et des lésions épidermiques. Le traitement par des doses élevées et/ou faibles d'UVA+UVB a également induit des lésions oxydatives de l'ADN et une cytotoxicité au niveau des FP humains. En outre, il a diminué la prolifération et favorisé l'apoptose de la gaine externe de la racine (ORS) du FP et des kératinocytes de la matrice des cheveux (MC), a stimulé le développement de la phase catagène, a régulé de manière différentielle l'expression des facteurs de croissance des FP, et induit une dégranulation périfolliculaire des mastocytes. Les lésions du FP médiées par les RUV étaient plus graves après une irradiation par dose élevée de RUV et atteignaient également les compartiments proximaux du FP. L'application topique de 0,1 % de caféine n'a pas induit de cytotoxicité de la peau ou du FP et a stimulé l'expression d'IGF-1 dans la partie proximale de l'ORS du FP. Cependant, elle a promu l'apoptose des kératinocytes dans certains compartiments de FP. En outre, la caféine a fourni une protection des FP contre la cytotoxicité et la dystrophie médiées par les RUV, l'apoptose des kératinocytes et une régulation à tendance positive de l'effet catagène induit par le facteur de croissance. CONCLUSION: Notre étude souligne la pertinence clinique de notre dosage d'irradiation UV ex vivo du cuir chevelu et fournit la première preuve que le rayonnement UV transépidermique affecte négativement d'importantes fonctions du FP chez l'homme. Cela suggère que l'intégration d'agents photoprotecteurs des FP tels que la caféine dans les formulations cosmétiques et nutraceutiques des écrans solaires pourrait constituer une stratégie prophylactique sensée.

Are melanocortin peptides future therapeutics for cutaneous wound healing?

Cutaneous wound healing is a complex process divided into different phases, that is an inflammatory, proliferative and remodelling phase. During these phases, a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year, it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds α-melanocyte-stimulating hormone (α-MSH) with high affinity and elicits pleiotropic biological effects, for example modulation of inflammation and immune responses, cytoprotection, antioxidative defense and collagen turnover. Truncated α-MSH peptides such as Lys-Pro-Val (KPV) as well as derivatives like Lys-d-Pro-Thr (KdPT), the latter containing the amino acid sequence 193-195 of interleukin-1ß, have been found to possess anti-inflammatory effects but to lack the pigment-inducing activity of α-MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so-far available data on melanocortin peptides and derivatives in wound healing.

Tropisetron via α7 nicotinic acetylcholine receptor suppresses tumor necrosis factor-α-mediated cell responses of human keratinocytes.

Tropisetron is a serotonin receptor (5-HT-R)-modulating agent and approved as an antiemetic for patients undergoing chemotherapy. In the gut, it acts via specific serotonin receptors, 5-HT3 -R, to elicit its beneficial effects against nausea. We investigated whether tropisetron can affect inflammatory cell responses of human primary epidermal keratinocytes (NHK) which are key cells in the regulation of skin homoeostasis. Tropisetron significantly and dose-dependently suppressed tumor necrosis factor (TNF)-α-mediated mRNA expression and protein secretion of interleukin (IL)-6 and IL-8 in these cells. This effect of tropisetron was independent of p65/NF-κB as shown by various NF-κB signal transduction read-outs. Importantly, the anti-inflammatory tropisetron effect on NHK was neither mediated by 5-HT3 -R nor 5-HT4 -R since these receptors were absent in NHK. In contrast, NHK expressed α7 nicotinic acetylcholine receptors (α7nAchR) which previously were found to bind tropisetron. The α7nAchR antagonist α-bungarotoxin neutralized, whereas AR-R17779, a specific α7nAchR agonist, mimicked the suppressive effect of tropisetron on TNF-α-mediated IL-6 and IL-8 expression in NHK. Our findings suggest that tropisetron and probably other α7nAchR-activating agents could be useful for the future therapy of inflammatory skin diseases.

Melatonin and Its Metabolites Ameliorate UVR-Induced Mitochondrial Oxidative Stress in Human MNT-1 Melanoma Cells.

Melatonin (Mel) is the major biologically active molecule secreted by the pineal gland. Mel and its metabolites, 6-hydroxymelatonin (6(OH)Mel) and 5-methoxytryptamine (5-MT), possess a variety of functions, including the scavenging of free radicals and the induction of protective or reparative mechanisms in the cell. Their amphiphilic character allows them to cross cellular membranes and reach subcellular organelles, including the mitochondria. Herein, the action of Mel, 6(OH)Mel, and 5-MT in human MNT-1 melanoma cells against ultraviolet B (UVB) radiation was investigated. The dose of 50 mJ/cm² caused a significant reduction of cell viability up to 48%, while investigated compounds counteracted this deleterious effect. UVB exposure increased catalase activity and led to a simultaneous Ca++ influx (16%), while tested compounds prevented these disturbances. Additional analysis focused on mitochondrial respiration performed in isolated mitochondria from the liver of BALB/cJ mice where Mel, 6(OH)Mel, and 5-MT significantly enhanced the oxidative phosphorylation at the dose of 10-6 M with lower effects seen at 10-9 or 10-4 M. In conclusion, Mel, 6(OH)Mel and 5-MT protect MNT-1 cells, which express melatonin receptors (MT1 and MT2) against UVB-induced oxidative stress and mitochondrial dysfunction, including the uncoupling of oxidative phosphorylation.