Current views on non-invasive in vivo determination of physiological parameters of the stratum corneum using confocal Raman microspectroscopy

Confocal Raman microspectroscopy is widely used in dermatology and cosmetology for analysis of the concentration of skin components (lipids, natural moisturizing factor molecules, water) and the penetration depth of cosmetic/medical formulations in the human stratum corneum (SC) in vivo. In recent years, it was shown that confocal Raman microspectroscopy can also be used for non-invasive in vivo depth-dependent determination of the physiological parameters of the SC, such as lamellar and lateral organization of intercellular lipids, folding properties of keratin, water mobility and hydrogen bonding states. The results showed that the strongest skin barrier function, which is primarily manifested by the orthorhombic organization of intercellular lipids, is provided at ≈20–40% SC depth, which is related to the maximal bonding state of water with surrounding components in the SC. The secondary and tertiary structures of keratin determine water binding in the SC, which is depth-dependent. This paper shows the technical possibility and advantage of confocal Raman microspectroscopy in non-invasive investigation of the skin and summarizes recent results on in vivo investigation of the human SC.

Impact of Water Exposure and Temperature Changes on Skin Barrier Function

The frequency of hand hygiene has increased due to the COVID-19 pandemic, but there is little evidence regarding the impact of water exposure and temperature on skin. The aim of this study is to evaluate the effect of water exposure and temperature on skin barrier function in healthy individuals. A prospective observational study was conducted. Temperature, pH, transepidermal water loss (TEWL), erythema and stratum corneum hydration (SCH) were measured objectively before and after hot- and cold-water exposure and TempTest® (Microcaya TempTest, Bilbao, Spain) contact. Fifty healthy volunteers were enrolled. Hot-water exposure increased TEWL (25.75 vs. 58.58 g·h−1·m−2), pH (6.33 vs. 6.65) and erythema (249.45 vs. 286.34 AU). Cold-water immersion increased TEWL (25.75 vs. 34.96 g·h−1·m−2) and pH (6.33 vs. 6.62). TEWL (7.99 vs. 9.98 g·h−1·m−2) and erythema (209.07 vs. 227.79 AU) increased after being in contact with the hot region (44 °C) of the TempTest. No significant differences were found after contact with the cold region (4 °C) of the TempTest. In conclusion, long and continuous water exposure damages skin barrier function, with hot water being even more harmful. It would be advisable to use cold or lukewarm water for handwashing and avoid hot water. Knowing the proper temperature for hand washing might be an important measure to prevent flares in patients with previous inflammatory skin diseases on their hands.

Impact of Exposome Factors on Epidermal Barrier Function in Patients with Obstructive Sleep Apnea Syndrome

Exposome factors, such as sleep deprivation and diet, could affect skin barrier function. The objectives of this study are to compare skin barrier function between patients with Obstructive Sleep Apnea Syndrome (OSAS) and healthy individuals, and to evaluate the effect of other exposome factors on skin. A cross-sectional study was conducted. Patients with OSAS and healthy volunteers matched by age and sex were included. OSAS severity was assessed by the Apnea-Hypopnea Index (AHI). Validated questionnaires were used to assess diet, anxiety, depression, and psychological stress. Skin barrier function parameters including temperature, erythema, melanin, pH, transepidermal water loss (TEWL), and stratum corneum hydration (SCH) were measured on the volar forearm. A total of 86 participants were included, 56 patients with OSAS and 30 healthy volunteers. TEWL was higher in OSAS patients than in healthy individuals (8.01 vs. 8.68 g·m−2·h−1). Regarding disease severity, severe patients had higher TEWL values (9.31 vs. 8.46 vs. 7.08 g·m−2·h−1) compared to moderate and mild patients. Patients with OSAS had significantly lower sleep quality (11.89 vs. 6.47 Pittsburgh Sleep Quality Index score; p < 0.001), poor adherence to the Mediterranean Diet (8.46 vs. 9.77; p = 0.005), and significantly higher anxiety and depression levels than healthy individuals. In conclusion, patients with OSAS may have skin barrier impairment, reflected in higher TEWL values. These patients also have higher levels of anxiety, depression, stress, and a lower adherence to a Mediterranean Diet, all exposome factors that might impact on skin barrier function.

Activated Protein C Protects against Murine Contact Dermatitis by Suppressing Protease-Activated Receptor 2

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with excessive inflammation and defective skin barrier function. Activated protein C (APC) is a natural anticoagulant with anti-inflammatory and barrier protective functions. However, the effect of APC on AD and its engagement with protease activated receptor (PAR)1 and PAR2 are unknown. Methods: Contact hypersensitivity (CHS), a model for human AD, was induced in PAR1 knockout (KO), PAR2KO and matched wild type (WT) mice using 2,4-dinitrofluorobenzene (DNFB). Recombinant human APC was administered into these mice as preventative or therapeutic treatment. The effect of APC and PAR1KO or PARKO on CHS was assessed via measurement of ear thickness, skin histologic changes, inflammatory cytokine levels, Th cell phenotypes and keratinocyte function. Results: Compared to WT, PAR2KO but not PAR1KO mice displayed less severe CHS when assessed by ear thickness; PAR1KO CHS skin had less mast cells, lower levels of IFN-γ, IL-4, IL-17 and IL-22, and higher levels of IL-1β, IL-6 and TGF-β1, whereas PAR2KO CHS skin only contained lower levels of IL-22 and IgE. Both PAR1KO and PAR2KO spleen cells had less Th1/Th17/Th22/Treg cells. In normal skin, PAR1 was present at the stratum granulosum and spinosum, whereas PAR2 at the upper layers of the epidermis. In CHS, however, the expression of PAR1 and PAR2 were increased and spread to the whole epidermis. In vitro, compared to WT cells, PAR1KO keratinocytes grew much slower, had a lower survival rate and higher para permeability, while PAR2KO cells grew faster, were resistant to apoptosis and para permeability. APC inhibited CHS as a therapeutic but not as a preventative treatment only in WT and PAR1KO mice. APC therapy reduced skin inflammation, suppressed epidermal PAR2 expression, promoted keratinocyte growth, survival, and barrier function in both WT and PAR1KO cells, but not in PAR2KO cells. Conclusions: APC therapy can mitigate CHS. Although APC acts through both PAR1 and PAR2 to regulate Th and mast cells, suppression of clinical disease in mice is achieved mainly via inhibition of PAR2 alone. Thus, APC may confer broad therapeutic benefits as a disease-modifying treatment for AD.

Skin Soothing Effect of Three Herbs from the Namwon-Mt.Jiri Regions

Purpose: This study was conducted to evaluate lavender, lemongrass, and peppermint grown in the Namwon-Mt.Jiri regions as functional soothing ingredients for cosmetics.Methods: The simultaneous analysis of 19 polyphenols in 50% ethanol-extracted samples of lavender, lemongrass, and peppermint cultivated in the Namwon-Mt.Jiri regions were analyzed by high-performance liquid chromatography (HPLC). Antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Using real-time PCR, improvements in skin barrier function were confirmed by observing the mRNA expression levels of filaggrin and involucrin, and the moisturizing ability was confirmed through the mRNA expression of HAS-2 and HAS-3. The anti-inflammatory efficacy was verified by confirming the expression levels of the inflammatory cytokine IL-6 and the pro-inflammatory mediator nitric oxide (NO).Results: In the simultaneous analysis of 19 phenolic compounds, rosmarinic acid from lavender; chlorogenic acid, syringic acid, p-coumaric acid, and ferulic acid from lemongrass; and caffeic acid, quercitin hydrate, rosmarinic acid, and hesperetin from peppermint were identified. Antioxidant efficacy was confirmed by DPPH radical scavenging, and excellent efficacy was shown in the order of lavender, peppermint, and lemongrass. Filaggrin and involucrin, skin barrier-related genes, were increased more in lavender, lemongrass, and peppermint than in the untreated group. HAS-2 and HAS-3 were also confirmed to be increased in lavender, lemongrass, and peppermint. Lavender, lemongrass, and peppermint all showed concentration-dependent inhibition of IL-6 and NO.Conclusion: Extracts of lavender, lemongrass, and peppermint cultivated in the Namwon-Mt.Jiri regions had excellent antioxidant, skin barrier, moisturizing and anti-inflammatory effects, so may be considered for use as natural raw materials for soothing cosmetics.

Potential of Tamanu (Calophyllum inophyllum) Oil for Atopic Dermatitis Treatment

Tamanu oil, derived from the nut of Calophyllum inophyllum L., has been traditionally used to treat various skin-related ailments. In recent years, this oil is increasingly gaining popularity as researchers continue to search for novel natural alternative therapies for various skin diseases. There have been a number of in vitro and in vivo studies investigating various skin-active properties of tamanu oil, and it has been proven to have potent anti-inflammatory, antioxidant, antimicrobial, analgesic, and even wound-healing abilities. These properties make tamanu oil an especially interesting candidate for the treatment of atopic dermatitis (AD). This multifaceted disease is marked by the disruption of the skin barrier function, chronic inflammation, and skin microbiome dysbiosis with limited treatment options, which is free from adverse events and inexpensive, making it desperate for a new treatment option. In this review, we examine previous in vitro and in vivo studies on AD-relevant pharmacological properties of tamanu oil in order to evaluate the potential of tamanu oil as a novel treatment option for AD.

Deacetylasperulosidic Acid Ameliorates Pruritus, Immune Imbalance, and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice

The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.

The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier

The skin barrier would not function without IL-1 family members, but their physiological role in the immunological aspects of skin barrier function are often overlooked. This review summarises the role of IL-1 family cytokines (IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37 and IL-38) in the skin. We focus on novel aspects of their interaction with commensals and pathogens, the important impact of proteases on cytokine activity, on healing responses and inflammation limiting mechanisms. We discuss IL-1 family cytokines in the context of IL-4/IL-13 and IL-23/IL-17 axis-driven diseases and highlight consequences of human loss/gain of function mutations in activating or inhibitory pathway molecules. This review highlights recent findings that emphasize the importance of IL-1 family cytokines in both physiological and pathological cutaneous inflammation and emergent translational therapeutics that are helping further elucidate these cytokines.