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Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 39504

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Special Issue Editors

Prof. Dr. Luis Monteiro Rodrigues

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Guest Editor

Universidade Lusófona – CBIOS Research Center for Biosciences and Health Technologies, 1749-024 Lisboa, Portugal
Interests: skin; skin physiology and pathology; vascular medicine and microcirculatory physiology; cosmetic dermatology; safety and efficacy of topical products; cardiovascular physiology; physiology; disease mechanisms

Dr. Bernard Querleux

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Guest Editor

L'Oréal Research and Innovation, Aulnay-sous-Bois, France
Interests: skin; hair; biophysics; noninvasive methods; multiphysics modeling; numerical simulation, high-performance computing; data science

Special Issue Information

Dear Colleagues,

The human skin currently plays a remarkable role in biomedical research. Generally accepted as a “window” to look further into multiple (pathophysiological) processes, it has also become a preferential screen to assess various functional indicators, in the very center of this new self- e-health assessment age.
Progress is recent, noted especially after the early 1980s, and driven (in part) by a new technological interest in novel assessment technologies and methodologies to characterize skin functions and mechanisms under a framework often termed as “skin biophysics”. There is also a multidisciplinary tradition in skin research. Contemporary visions and contributions from physiology, molecular immunology, computational engineering, and electronics, among others, have transformed skin research into a uniquely transversal, multicollaborative hub that continues to develop and attract scientists from many different domains all over the world.
The present Special Issue, titled “Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances,” edited by Life and led by Professor Monteiro Rodrigues and Dr. Bernard Querleux, aims to bring together different views from different backgrounds, from novel approaches to classic variables (e.g., epidermal hydration, “barrier” functions, skin microcirculation) to new viewpoints (e.g., the “gut–skin axis”, cutaneous circadian rhythms, nutritional impacts) and determinants beyond age, sex and race. Skin Homeostasis is at the cutting edge of modern skin research and involves an enormous application potential—from basic knowledge, new drugs, and health products to wearables and state-of-the-art diagnostics systems. We wish to gather leading related research that will impact many different applicational domains.
The (non-exhaustive) keywords listed here illustrate the diversity of expected topics.
Please visit the Instructions for Authors page before submitting your review or original manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Significant special discounts are offered to invited authors.
Submitted papers should be well formatted and use good English. Authors may use MDPI’s English editing service prior to publication or during author revisions. For more information, please refer to https://www.mdpi.com/journal/life/special_issues/Skin_Epidermis.

Prof. Dr. Luis Monteiro Rodrigues
Dr. Bernard Querleux
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

aging
health
repair
disease
exposome
microbiome
skin barrier
chronobiology
inflammation
mechanobiology
intra-/intercellular crosstalk
macrophage
stem cells
reconstructed skin
computational methods
noninvasive methods
imaging
smart devices

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Published Papers (11 papers)

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Research

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8 pages, 1232 KiB

Open AccessCommunication

Effect of an Emollient Emulsion Containing 15.0% of Caprylic/Capric Triglyceride on the Urocanic Acid of the Stratum Corneum

by Alicio Vitorino de Souza Neto, Débora Quintas Balla, Thalita Marcilio Candido, Catarina Rosado, André Rolim Baby and Fabiana Vieira Lima Solino Pessoa

Life 2023, 13(4), 876; https://doi.org/10.3390/life13040876 - 25 Mar 2023

Cited by 7 | Viewed by 3119

Abstract

Natural moisturizing factor (NMF) includes several compounds in the stratum corneum (SC), among them, urocanic acid (UCA). Ultraviolet (UV) exposure turns the trans-UCA of the SC into its cis isomer. We investigated the impact of a topical emollient emulsion treatment on the UCA isomers of the SC exposed to artificial UV stress. Aliquots of emollient emulsion were applied in healthy subjects for 2 h on delimited areas of the volar forearm, then, the SC was removed by tape stripping. Tapes were irradiated in a solar simulator chamber and a high performance liquid chromatograph was used to quantify UCA isomers from stripped SC extract. The amount of both UCA isomers were almost twice higher in the SC treated with the emollient emulsion. We also observed that the UV irradiation elevated the amount of the cis/trans UCA ratio on the SC (non-treated and treated), suggesting that the emollient sample was not able to avoid the UCA isomerization. The in vivo tests corroborated with the UCA data obtained ex vivo, since we found an increase in the superficial skin hydration with respective reduction of the TEWL, probably occurring by the occlusion performed by the emollient emulsion containing 15.0% w/w of caprylic/capric triglyceride. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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13 pages, 3076 KiB

Open AccessArticle

Evaluation of Morphological and Structural Skin Alterations on Diabetic Subjects by Biophysical and Imaging Techniques

by Veronica Rego Moraes, Maisa Oliveira Melo and Patrícia M. B. G. Maia Campos

Life 2023, 13(2), 579; https://doi.org/10.3390/life13020579 - 18 Feb 2023

Cited by 3 | Viewed by 2812

Abstract

Diabetes causes increased production of advanced glycation end products (AGEs), which may lead to irreversible damage to collagen fibers, and early and more accentuated signs of skin aging. Thus, the objective of this study was to evaluate diabetic skin’s mechanical and morphological characteristics and compare these to healthy skin. Twenty-eight female participants aged between 39 and 55 years were enrolled: half had type 2 diabetes, and the others were healthy. Wrinkles, transepidermal water loss (TEWL), stratum corneum water content, skin color, elasticity, morphological and structural characteristics of epidermis and dermis echogenicity were evaluated using biophysical and skin imaging techniques. Higher TEWL values were observed in participants with diabetes, who also showed lower skin elasticity and wrinkles with greater volume, area, and depth. In addition, the Reflectance Confocal Microscopy (RCM) imaging analysis showed that all participants with diabetes presented polycyclic papillae and deformed and amorphous collagen fibers. The obtained data showed significant differences between healthy and diabetic skin and could help develop more specific topical treatments to improve the treatment of skin conditions in people with diabetes. Finally, RCM is an advanced imaging technique that allows for a more profound analysis of diabetic skin, which could assist in the evaluation of dermocosmetic treatments to improve the skin alterations caused by this disease. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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20 pages, 1911 KiB

Open AccessArticle

Development of a Nanotechnology Matrix-Based Citronella Oil Insect Repellent to Obtain a Prolonged Effect and Evaluation of the Safety and Efficacy

by Celio Takashi Higuchi, Caroline Cianga Sales, Newton Andréo-Filho, Tereza Silva Martins, Helena Onishi Ferraz, Yasmin Rosa Santos, Patricia Santos Lopes, Jeffrey Ernest Grice, Heather Ann Elizabeth Benson and Vania Rodrigues Leite-Silva

Life 2023, 13(1), 141; https://doi.org/10.3390/life13010141 - 4 Jan 2023

Cited by 6 | Viewed by 4945

Abstract

Mosquito-borne diseases affect millions of people worldwide each year, and the use of a topically applied insect repellent is an economically viable preventative health practice. The general objective of this work was to encapsulate citronella oil (CO) in a nanostructured lipid carrier (NLC) to formulate a topical repellent with a long duration of efficacy on the skin and a good safety profile based on minimizing skin penetration. In the studied CO, the main chemical constituents of geraniol, citronellal, and citronellol were identified and subsequently used as markers for the in vitro skin permeation testing (IVPT). An optimal NLC encapsulating CO formulation was developed and had an average particle size of 350 nm. The NLC was then formulated in combination with CO at ratios of 2:1, 1:1, and 1:2 CO:NLC-CO as oil-in-water (O/W) emulsions and compared to CO in the same O/W emulsion base (all at 10% CO in the final O/W topical formulation). The markers geraniol, citronellol, and citronellal were detected in all samples tested F1 (10% CO in O/W emulsion) and F3 (10% CO/NLC-CO 1:1 in O/W emulsion). Even the percentages of F3 markers were higher than F1. The recovery of the percentage balance (based on the total remaining on the skin surface, on the skin, and penetrated through the skin to the receptor) of geraniol, citronellol, and citronellal markers for F1 and F3 was 7.70% and 11.96%; 25.51% and 31.89%; and 5.09% and 4.40%, respectively. The nanoparticle lipid solid forms a repellent reservoir on the skin surface, releasing the active ingredients slowly through volatilization, extending the repellent action, and reducing permeation through the skin. It is possible to assume that the remaining 92.30% and 88.03%; 74.49% and 68.11%; and 94.10% and 95.60% of geraniol, citronellol, and citronellal markers of F1 and F3, respectively, were lost to evaporation. In the in vivo efficacy test carried out with the Aedes aegypti mosquito, F3 was the optimal formulation, providing the greatest repellent action compared to free oil in O/W emulsion. Thermal analysis showed that the NLC-CO raised the boiling point of the encapsulated CO compared to the free oil, suggesting that the controlled release of the CO was a possible mechanism for its prolonged effect. We concluded that the nanocarriers developed with CO were stable and provided improved mosquito-repellent efficacy with minimal skin penetration of the CO actives over 24 h. Indeed, regardless of whether the CO was applied as free oil, a 1:1 mixture of CO (pure/free oil) or NLC-CO applied in an O/W emulsion can be considered safe for topical application due to minimal skin penetration. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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13 pages, 3518 KiB

Open AccessArticle

Hydrolipidic Characteristics and Clinical Efficacy of a Dermocosmetic Formulation for the Improvement of Homeostasis on Oily Mature Skin

by Letícia Kakuda, Maísa Oliveira de Melo and Patrícia Maria Berardo Gonçalves Maia Campos

Life 2023, 13(1), 87; https://doi.org/10.3390/life13010087 - 28 Dec 2022

Cited by 3 | Viewed by 2113

Abstract

Background: Although the scientific literature associates mature skin with dry skin and the secretion of sebum on the face decreases over the years, in tropical countries, such as Brazil, mature skin can still present oily characteristics. Thus, the knowledge of the hydrophilic characteristics of mature skin is fundamental to help the development of more effective treatments for this skin type. In this context, the study aimed to evaluate the hydrophilic characteristics and the clinical efficacy of a cosmetic formulation for mature skin added with alfalfa and lentil extracts by using biophysical and skin imaging techniques. Methods: Twenty-eight healthy females aged between 45 and 59 years were enrolled. Measurements of the stratum corneum water content, sebum content, transepidermal water loss, skin microrelief, and pores count were performed before and after the 28-day formulation application. Results: The mature skin presented as oily with wrinkles and pores. The proposed formulation significantly reduced the sebum content and the number of fine and large pores and improved skin microrelief and hydration after a 28-day period of the application when compared to the vehicle. Conclusions: The proposed formulation was effective in oily mature skin treatment, improving its general skin aging and oiliness conditions, and reducing pores count in just 28 days. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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9 pages, 1421 KiB

Open AccessArticle

Optoacoustic Imaging Offers New Insights into In Vivo Human Skin Vascular Physiology

by Luis Monteiro Rodrigues, Tiago F. Granja and Sergio Faloni de Andrade

Life 2022, 12(10), 1628; https://doi.org/10.3390/life12101628 - 18 Oct 2022

Cited by 7 | Viewed by 2033

Abstract

Functional imaging with new photoacoustic tomography (PAT) offers improved spatial and temporal resolution quality in in vivo human skin vascular assessments. In the present study, we followed a suprasystolic reactive hyperemia (RH) maneuver with a multi-spectral optoacoustic tomography (MSOT) system. A convenience sample of ten participants, both sexes, mean age of 35.8 ± 13.3 years old, was selected. All procedures were in accordance with the principles of good clinical practice and approved by the institutional ethics committee. Images were obtained at baseline (resting), during occlusion, and immediately after pressure release. Observations of the RH by PAT identified superficial and deeper vascular structures parallel to the skin surface as part of the human skin vascular plexus. Furthermore, PAT revealed that the suprasystolic occlusion impacts both plexus differently, practically obliterating the superficial smaller vessels and evoking stasis at the deeper, larger structures in real-time (live) conditions. This dual effect of RH on the skin plexus has not been explored and is not considered in clinical settings. Thus, RH seems to represent much more than the local microvascular reperfusion as typically described, and PAT offers a vast potential for vascular clinical and preclinical research. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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9 pages, 792 KiB

Open AccessArticle

The Impact of Kefir on Epidermal Water Homeostasis in Healthy Human Skin

by Emília Alves, João Gregório, Patrícia Rijo, Catarina Rosado and Luís Monteiro Rodrigues

Life 2022, 12(7), 1075; https://doi.org/10.3390/life12071075 - 19 Jul 2022

Cited by 4 | Viewed by 2145

Abstract

Kefir, a symbiotic consortium of diverse bacteria and yeasts, is one of the most popular probiotic foods on the market. Its consumption has been referred to as beneficial in human skin health, namely in the reinforcement of skin’s barrier function. This benefit likely results from the productive activity of lactic acid bacteria during kefir fermentation. Lactic acid is naturally present in the skin, and actively contributes to epidermal water dynamics and “barrier.” Few studies have been conducted regarding the impact of probiotic consumption in human epidermal water homeostasis. Therefore, this study was designed to explore the impact of the regular consumption of kefir on the skin water dynamics in a group of participants with healthy skin. Participants (n = 27) were healthy female volunteers from whom twelve consumed 100 mL of kefir every day for eight weeks as part of their diet. The remaining (untreated) participants served as the control group. Epidermal water balance was assessed by measuring transepidermal water loss (TEWL) and stratum corneum (SC) hydration on three different occasions—at baseline (T0), after four weeks (T4) and after eight weeks (T8) of interventive kefir consumption. Our study revealed a significant reduction in TEWL (p = 0.043) in the kefir group after eight weeks of regular consumption. In the same period, no differences were found for TEWL in the control group (p = 0.997). Regarding hydration, skin dryness was progressive in the control group, with a significant reduction in SC hydration (p = 0.002) at T8 in comparison to T0. In the kefir group, SC hydration was preserved between T0 and T8 (p = 0.997), which we believe to be related to epidermal “barrier” reinforcement. Our study seems to confirm that the regular consumption of kefir does improve cutaneous water balance even in healthy skin. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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9 pages, 3858 KiB

Open AccessArticle

Assessing the Role of Carbonyl Adducts, Particularly Malondialdehyde Adducts, in the Development of Dermis Yellowing Occurring during Skin Photoaging

by Hélène Zucchi, Hervé Pageon, Daniel Asselineau, Marion Ghibaudo, Inês Sequeira and Sarah Girardeau-Hubert

Life 2022, 12(3), 403; https://doi.org/10.3390/life12030403 - 10 Mar 2022

Cited by 7 | Viewed by 3515

Abstract

Solar elastosis is associated with a diffuse yellow hue of the skin. Photoaging is related to lipid peroxidation leading to the formation of carbonyl groups. Protein carbonylation can occur by addition of reactive aldehydes, such as malondialdehyde (MDA), 4-hydroxy-nonenal (4-HNE), and acrolein. All the proteins concerned with this modification, and the biological consequences of adduct formation, are not completely identified. The link between yellowish skin and dermal carbonylated proteins induced by aldehyde adducts was investigated. The study was carried out on ex vivo skin samples from sun-exposed or sun-protected areas and on in vitro dermal equivalent models incubated with 5 mM MDA, 4-HNE, or acrolein. The yellow color and the level of MDA, 4-HNE, and acrolein adducts were evaluated. Yellowish color differences were detected in the dermis of sun-exposed skin compared to sun-protected skin and in in vitro models following addition of MDA, 4-HNE, or acrolein. The yellowing was correlated with the carbonyl adducts increasing in the dermis and in in vitro models incubated with aldehydes. The stronger yellowing seemed to be mediated more by MDA than 4-HNE and acrolein. These observations suggest that dermal carbonylation especially induced by MDA result in the yellow hue of dermis and is involved, in part, in the yellowing observed during skin photoaging. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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14 pages, 2745 KiB

Open AccessArticle

Epidermal Barrier Function and Skin Homeostasis in Atopic Dermatitis: The Impact of Age

by Trinidad Montero-Vilchez, Carlos Cuenca-Barrales, Juan-Angel Rodriguez-Pozo, Pablo Diaz-Calvillo, Jesús Tercedor-Sanchez, Antonio Martinez-Lopez, Alejandro Molina-Leyva and Salvador Arias-Santiago

Life 2022, 12(1), 132; https://doi.org/10.3390/life12010132 - 17 Jan 2022

Cited by 29 | Viewed by 3516

Abstract

Skin is damaged in atopic dermatitis (AD) patients. Age is also believed to have a negative effect on epidermal barrier function. The aim of this study was to investigate skin barrier function changes with age in AD patients. A cross-sectional study was conducted including 162 participants, 81 AD patients and 81 healthy volunteers. Skin barrier function parameters, such as transepidermal water loss (TEWL), erythema, temperature, stratum corneum hydration (SCH), pH, and elasticity, were evaluated. Healthy volunteers were evaluated on the volar forearm. AD patients were measured on two regions: on an eczematous lesion on the volar forearm and on a non-involved area 5 cm from the affected area. TEWL was lower on healthy skin than uninvolved AD skin (9.98 vs. 25.51 g·m⁻²·h⁻¹, p < 0.001) and AD eczematous lesions (9.98 vs. 28.38 g·m⁻²·h⁻¹, p < 0.001). SCH was lower on AD eczematous lesions than uninvolved AD skin (24.23 vs. 39.36 AU, p < 0.001) and healthy skin (24.23 vs. 44.36 AU, p < 0.001). Elasticity was lower on AD eczematous lesions than uninvolved AD skin (0.69 vs. 0.74, p = 0.038) and healthy skin (0.69 vs. 0.77, p = 0.014). A negative correlation was found between age and elasticity in all the population (r = −0.383, p < 0.001). This correlation was stronger in AD patients (r = −0.494, p < 0.001) than in controls (r = −0.266, p = 0.092). After conducting a linear regression model in AD patients adjusted by age, sex, and SCORing Atopic Dermatitis (SCORAD), it was found that elasticity was impaired by an increasing age (β = −0.004, p < 0.001) and a higher SCORAD (β = −0.003, p < 0.001). The skin barrier function is impaired by age and AD, reflected mainly in poor elasticity values in older AD patients. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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11 pages, 11555 KiB

Open AccessArticle

Biological Efficacy Evaluation of a Non-Cross-Linked Hyaluronic Acid Dermal Filler for Biomedical Application in Inflammatory Scalp Conditions

by Sabrina Sommatis, Maria Chiara Capillo, Elsa Liga, Cristina Maccario, Raffaele Rauso, Martha Herrera, Nicola Zerbinati and Roberto Mocchi

Life 2022, 12(1), 2; https://doi.org/10.3390/life12010002 - 21 Dec 2021

Viewed by 3180

Abstract

(1) Background: The dysbiosis of some cutaneous commensal microorganisms is the trigger factor for the activation of the inflammatory cascade by keratinocytes in many skin disorders. Mesotherapy is an innovative technique for many scalp disorders, with the function of restoring the physiology of the skin. (2) Methods: the antimicrobial, antibiofilm and anti-inflammatory activity of the non-cross-linked HA formulation (Hydro Deluxe, Matex Lab S.p.a., Brindisi, Italy) was investigated against the most common microorganisms of the scalp (Staphyloccoccus epidermis, Staphyloccoccus aureus, Cutibacterium acnes and Malassezia furfur). Anti-inflammatory activity was evaluated on an internal 3D model of Reconstructed Human Epidermis (RHE) inserts infected with the strains as pro-inflammatory stimulus. (3) Results and Conclusions: the data collected showed a good antimicrobial and antibiofilm activity against all selected strains. The HA-based formulation did not show cytotoxicity on RHE, either alone or in presence of the infectious stimulus. The analysis of the expression of Interleukin (IL)-8 levels showed an excellent ability to reduce this pro-inflammatory marker. Overall, the efficacy assessment of the formulation supported its potential effectiveness in mesotherapy for the treatment of scalp disorders. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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Review

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11 pages, 916 KiB

Open AccessReview

The Trinity of Skin: Skin Homeostasis as a Neuro–Endocrine–Immune Organ

by Rong Jin, Lan Luo and Jie Zheng

Life 2022, 12(5), 725; https://doi.org/10.3390/life12050725 - 12 May 2022

Cited by 20 | Viewed by 7605

Abstract

For a long time, skin was thought to be no more than the barrier of our body. However, in the last few decades, studies into the idea of skin as an independent functional organ have gradually deepened our understanding of skin and its functions. In this review, we gathered evidence that presented skin as a “trinity” of neuro–endocrine–immune function. From a neuro perspective, skin communicates through nerves and receptors, releasing neurotrophins and neuropeptides; from an endocrine perspective, skin is able to receive and secrete most hormones and has the cutaneous equivalent of the hypothalamic-pituitary-adrenal (HPA) axis; from an immune perspective, skin is protected not only by its physical barrier, but also immune cells and molecules, which can also cause inflammation. Together as an organ, skin works bidirectionally by operating peripheral neuro–endocrine–immune function and being regulated by the central nervous system, endocrine system and immune system at the same time, maintaining homeostasis. Additionally, to further explain the “trinity” of cutaneous neuro–endocrine–immune function and how it works in disease pathophysiology, a disease model of rosacea is presented. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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20 pages, 967 KiB

Open AccessReview

Challenges and Opportunities for the Translation of Single-Cell RNA Sequencing Technologies to Dermatology

by Alex M. Ascensión, Marcos J. Araúzo-Bravo and Ander Izeta

Life 2022, 12(1), 67; https://doi.org/10.3390/life12010067 - 4 Jan 2022

Cited by 7 | Viewed by 3521

Abstract

Skin is a complex and heterogeneous organ at the cellular level. This complexity is beginning to be understood through the application of single-cell genomics and computational tools. A large number of datasets that shed light on how the different human skin cell types interact in homeostasis—and what ceases to work in diverse dermatological diseases—have been generated and are publicly available. However, translation of these novel aspects to the clinic is lacking. This review aims to summarize the state-of-the-art of skin biology using single-cell technologies, with a special focus on skin pathologies and the translation of mechanistic findings to the clinic. The main implications of this review are to summarize the benefits and limitations of single-cell analysis and thus help translate the emerging insights from these novel techniques to the bedside. Full article

(This article belongs to the Special Issue Skin Homeostasis: Mechanisms, Communication Routes, and Imbalances)

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