The Protective Effect of Carotenoids, Polyphenols, and Estradiol on Dermal Fibroblasts under Oxidative Stress

Skin ageing is influenced by several factors including environmental exposure and hormonal changes. Reactive oxygen species (ROS), which mediate many of the effects of these factors, induce inflammatory processes in the skin and increase the production of matrix metalloproteinases (MMPs) in dermal fibroblasts, which leads to collagen degradation. Several studies have shown the protective role of estrogens and a diet rich in fruits and vegetables on skin physiology. Previous studies have shown that dietary carotenoids and polyphenols activate the cell’s antioxidant defense system by increasing antioxidant response element/Nrf2 (ARE/Nrf2) transcriptional activity and reducing the inflammatory response. The aim of the current study was to examine the protective effect of such dietary-derived compounds and estradiol on dermal fibroblasts under oxidative stress induced by H2O2. Human dermal fibroblasts were used to study the effect of H2O2 on cell number and apoptosis, MMP-1, and pro-collagen secretion as markers of skin damage. Treatment of cells with H2O2 led to cell death, increased secretion of MMP-1, and decreased pro-collagen secretion. Pre-treatment with tomato and rosemary extracts, and with estradiol, reversed the effects of the oxidative stress. This was associated with a reduction in intracellular ROS levels, probably through the measured increased activity of ARE/Nrf2. Conclusions: This study indicates that carotenoids, polyphenols, and estradiol protect dermal fibroblasts from oxidative stress-induced damage through a reduction in ROS levels.

A Review on the Antioxidant and Antiaging Properties of White Tea

The present review explored to extend the current knowledge by highlighting the antioxidative and antiaging profile of white tea. White tea, the least processed of the teas, is one of the least investigated and has the highest phenolic content. The white tea has a great potential on the skin for cosmetics and the for better skin physiology. Tea polyphenols, particularly catechin derivatives, are powerful antioxidants that benefit human health. Because of their potential to scavenge free radicals and thereby prevent oxidative stress, antioxidant components have piqued interest. In this context, several studies have revealed antiaging activity of white tea, as it involved in preventing aging and other age-related disorders. White tea delays the process of aging and improves the longevity of life. This manuscript provides a summary of various bioactive components present in white tea along with the different alkaloids, enriched with (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin 3-gallate (EGCG), which are responsible for their health-promoting and antiaging properties.

Growth Hormone and the Human Hair Follicle

Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of the hypothalamic-pituitary-thyroid axis, and even generate melatonin and prolactin, human hair research has proven to be a treasure chest for the exploration of neurohormone functions. However, growth hormone (GH), one of the dominant neurohormones of human neuroendocrine physiology, remains to be fully explored in this context. This is interesting since it has long been appreciated clinically that excessive GH serum levels induce distinct human skin pathology. Acromegaly, or GH excess, is associated with hypertrichosis, excessive androgen-independent growth of body hair, and hirsutism in females, while dysfunctional GH receptor-mediated signaling (Laron syndrome) is associated with alopecia and prominent HF defects. The outer root sheath keratinocytes have recently been shown to express functional GH receptors. Furthermore, and contrary to its name, recombinant human GH is known to inhibit female human scalp HFs’ growth ex vivo, likely via stimulating the expression of the catagen-inducing growth factor, TGF-β2. These limited available data encourage one to systematically explore the largely uncharted role of GH in human HF biology to uncover nonclassical functions of this core neurohormone in human skin physiology.

Acidic Skin Care Promotes Cutaneous Microbiome Recovery And Skin Physiology in An Acute Stratum Corneum Stress Model

Background: The skin microbiome and skin physiology are important indicators of the epidermal homeostasis status. Stress models are used to reveal pathological conditions and modulating effects. The recovery phase served to investigate the cutaneous microbiome in relation to skin physiology after mild tape stripping without treatment compared to two cosmetic leave-on lotions (pH 5.5 vs. pH 9.3). Material and MethodsThe prospective, randomized, controlled study was performed in 25 healthy volunteers: The microbiome was assessed via swabs and subsequent 16S-rRNA-gene amplicon sequencing. Skin physiology was analyzed in terms of barrier function, stratum corneum hydration, surface-pH, skin color non-invasively. All parameters were assessed before and immediately after 2hrs., 2 days and 7 days after tape stripping. Lotion A (pH 5.5) and the identical lotion B (pH 9.3) were applied 2-times per day for 7 days on the volar forearm.ResultsTape stripping reduced the alpha diversity with a recovery over 7 days without treatment. Both lotions significantly accelerated the recovery of the alphadiversity already after 2 days with a slightly higher rate for lotion A (pH 5.5). After tape stripping, the relative abundance of Proteobacteria was increased, whereas Actinobacteria were reduced. Further, mean relative abundances of typical skin-associated genera were reduced after tape stripping. Taxa compositions returned to normal levels after 7 days in all treatment groups, and an accelerated normalization could be observerd with treatment by both lotions already after tow days. A significant difference in skin-pH was observed at day2 and day7 with an increased pH in lotion B treatment. Both lotions induced an increase in stratum corneum hydration. Barrier function was only changed by tape stripping. DiscussionThe study proved the suitability of an experimental stress model in the assessment of skin surface microbiome in relation to skin physiology. Stratum corneum hydration increased significantly with both lotions already at day 2. Microbiome parameters (alpha-diversity, mean relative taxa, abundance of selected genera) normalized over 2-7 days. Three potential mechanisms could be responsible for the accelerated normalization: a) optimized hydration during the recovery phase b) the composition of the lotion, c) acidic pH of the lotion.

Characterization of Cowhage-induced Pruritus in Sensitive Skin: An Observational Laboratory Study

Sensitive skin is a prevalent syndrome, characterized by discomfort in response to mild stimuli, which impacts life quality. Its pathomechanism remains insufficiently understood. Pruritus is one of the major symptoms. As one of the experimental models for pruritus, the cowhage skin prick test might provide an insight to the understanding of sensitive skin. This study aimed to specify the characteristics of cowhage-induced pruritus in sensitive skin. 20 female sensitive skin volunteers and 20 controls were recruited. Self-report questionnaires were distributed and their responses evaluated; moreover, alongside assessments by dermatologists, skin physiology assessments, lactic acid sting test, capsaicin test and cowhage skin challenge were performed. This study showed that pruritus in sensitive skin is perceived as more intense and longer-lasting, with different qualities of accompanying sensations than in normal skin. Test results of cowhage skin challenge showed moderate consistency with clinical assessments. The results suggest that cowhage skin challenge could be a new tool for sensitive skin assessment.

Chronic overexpression of neuropeptide Y in the skin is sufficient to induce inflammation and epidermal and dermal pathology

Neuropeptide Y (NPY) is a pleiotropic peptide produced in the central nervous system and peripheral organs. Despite conjectures that NPY may have a role in skin physiology and pathology, the effects of NPY in this organ remain poorly understood. We reported that a knock-in mouse with entopic NPY overexpression exhibits significantly elevated NPY in the skin, accompanied by premature and progressive hair graying secondary to depletion of melanocyte stem cells within hair follicles. However, the question remains as to whether NPY overexpression in the skin can induce non-melanocyte pathology. In this study, we employed this mouse to investigate the consequences of skin-specific overexpression of NPY. Our findings show that chronic NPY overexpression in the skin induces dermal fibrosis and epidermal hyperkeratosis. Additionally, NPY overexpression induces significant accumulation of macrophages and regulatory T cells in the dermis. RNA sequencing of whole skin from NPY-overexpressing mice further reveals NPY-mediated transcriptional changes consistent with inflammatory processes and inflammation-associated skin changes and highlights novel cell types involved in the NPY-mediated response in the skin. Together, these results provide long-awaited evidence of NPY’s involvement in skin pathology, providing a background for defining the precise role of NPY in the regulation of cutaneous homeostasis and disease.

Anti-Photoaging and Anti-Inflammatory Effects of Ginsenoside Rk3 During Exposure to UV Irradiation

Ginseng is a widely cultivated perennial plant in China and Korea. Ginsenoside Rk3 is one of the major active components of ginseng and is a promising candidate to regulate skin pigments and exert anti-photoaging effects on skin physiology. Ginsenoside Rk3 was mixed with a cream (G-Rk3 cream) and smeared on the skin of mice. Then, the mice were exposed to ultraviolet (UV) A (340 nm and 40 W) and UVB (313 nm and 40 W) radiation. Special attention was given to the anti-photoaging and anti-inflammatory effects of ginsenoside Rk3 on the mouse skin. Macroscopic evaluation indicated that the mouse dorsal skin looked smooth and plump even under UV irradiation for 12 weeks. Pathological analysis indicated that there was no obvious photoaging or inflammation in the mouse skin that was treated with the G-Rk3 cream. More healthy, intact, and neat collagen fibers were observed in mice treated with the G-Rk3 cream than in untreated mice. Further analysis proved that ginsenoside Rk3 could inhibit the decrease in water and hydroxyproline levels in skin tissues and the loss of superoxide dismutase and glutathione peroxidase activities in the blood. Moreover, ginsenoside Rk3 slowed or halted increases in malondialdehyde, matrix metalloproteinase (MMP)-1, and MMP-3 levels in the blood and levels of interleukin 1, interleukin 6, and tumor necrosis factor α in skin tissues. In conclusion, ginsenoside Rk3 plays a significant role in inhibiting photoaging and inflammation to protect skin health.

An In Vitro Mixed Infection Model With Commensal and Pathogenic Staphylococci for the Exploration of Interspecific Interactions and Their Impacts on Skin Physiology

The skin microbiota has been recognized to play an integral role in the physiology and pathology of the skin. The crosstalk between skin and the resident microbes has been extensively investigated using two-dimensional (2D) and three-dimensional (3D) cell cultures in vitro; however, skin colonization by multiple species and the effects of interspecific interactions on the structure and function of skin remains to be elucidated. This study reports the establishment of a mixed infection model, incorporating both commensal (Staphylococcus epidermidis) and pathogenic (Staphylococcus aureus) bacteria, based on a 3D human epidermal model. We observed that co-infecting the 3D epidermal model with S. aureus and S. epidermidis restricted the growth of S. aureus. In addition, S. aureus induced epidermal cytotoxicity, and the release of proinflammatory cytokines was attenuated by the S. aureus-S. epidermidis mixed infection model. S. epidermidis also inhibited the invasion of the deeper epidermis by S. aureus, eliciting protective effects on the integrity of the epidermal barrier. This 3D culture-based mixed infection model would be an effective replacement for existing animal models and 2D cell culture approaches for the evaluation of diverse biotic and abiotic factors involved in maintaining skin health.

Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity

In this study, we used the zebrafish animal model to establish a bioassay by which physiological efficacy differential of alpha-melanocyte-stimulating hormone (α-MSH) analogues could be measured by melanosome dispersion in zebrafish larvae. Brain-skin connection research has purported the interconnectedness between the nervous system and skin physiology. Accordingly, the neuropeptide α-MSH is a key regulator in several physiological processes, such as skin pigmentation in fish. In mammals, α-MSH has been found to regulate motivated behavior, appetite, and emotion, including stimulation of satiety and anxiety. Several clinical and animal model studies of autism spectrum disorder (ASD) have already demonstrated the effectiveness of α-MSH in restoring the social deficits of autism. Therefore, we sought to analyze the effect of synthetic and naturally-occurring α-MSH variants amongst different species. Our results showed that unique α-MSH derivatives from several fish species produced differential effects on the degree of melanophore dispersion. Using α-MSH human form as a standard, we could identify derivatives that induced greater physiological effects; particularly, the synthetic analogue melanotan-II (MT-II) exhibited a higher capacity for melanophore dispersion than human α-MSH. This was consistent with previous findings in an ASD mouse model demonstrating the effectiveness of MT-II in improving ASD behavioral symptoms. Thus, the melanophore assay may serve as a useful screening tool for therapeutic candidates for novel drug discovery.

Genetic and climatic factors in the dispersal of Anatomically Modern Humans Out of Africa

The evolutionarily recent dispersal of Anatomically Modern Humans (AMH) out of Africa and across Eurasia provides an opportunity to study rapid genetic adaptation to multiple new environments. Genomic analyses of modern human populations have detected limited signals of strong selection such as hard sweeps, but genetic admixture between populations is capable of obscuring these patterns and is well known in recent human history, such as during the Bronze Age4. Here we show that ancient human genomic datasets contain multiple genetic signatures of strong selection including 57 hard sweeps, many with strong associations with cold adaptation. Similar genetic signatures of adaptation are also observed in adaptively-introgressed archaic hominin loci, as well as modern Arctic human groups. Consistent targets include the regulation of fat storage, skin physiology, cilia function and neural development; with multiple associations to modern western diseases. The spatiotemporal patterns of the hard sweeps allow reconstruction of early AMH population dispersals, and reveal a prolonged period of genetic adaptation (~80-50,000 years) following their initial out of Africa movement, before a rapid spread across Eurasia reaching as far as Australia.