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Simple Summary: This study focused on young Chinese women to investigate the variations in skin surface lipids and physiological parameters, such as moisture and temperature, over a 24 h period. By collecting the skin surface lipids' amplitudes and measuring the physiological parameters at seven time points within 24 h, we identified significant circadian rhythmic changes in four major lipid classes and seven lipid subclasses. Additionally, we revealed a significant correlation between key lipids associated with skin barrier function and physiological parameters. The findings underscore the crucial role of skin surface lipids' circadian rhythms in maintaining skin barrier health, providing a scientific foundation for the development of targeted skincare solutions that align with the body's natural biological rhythms. Background: Circadian rhythms are driven by the biological clock, an endogenous oscillator that generates approximately 24 h cycles in mammals. The circadian regulation of the lipid metabolism plays a crucial role in overall metabolic health. An analysis of the correlation between the skin's physiological parameters and skin lipids can provide a better insight into the rhythmic changes in skin condition. Objectives: The aim was to reveal how skin surface lipids (SSLs) participate in the regulation of circadian rhythms in the skin and the importance of the circadian oscillation of facial lipid molecules in maintaining epidermal homeostasis. Methods: Changes in SSLs were assessed using UPLC-QTOF-MS. The skin's physiological parameters were quantified using non-invasive instruments. Multivariate data analysis was employed to evaluate the differences. Results: Both skin surface lipids and physiological parameters exhibited certain circadian variation patterns. Four major lipid classes (fatty acids, glycerophospholipids, prenol lipids, saccharolipids) exhibited circadian rhythmic trends, with seven lipid subclasses contributing most significantly to the overall patterns observed. Among the physiological parameters assessed, sebum secretion, transepidermal water loss, moisture measurement value, and skin surface temperature exhibited sinusoidal circadian rhythms. Further analysis revealed significant correlations between fatty acids and saccharolipids with moisture measurement values, and between glycerolipids and pH value. In addition, lipids closely associated with the barrier such as unsaturated fatty acids and ceramide chain lengths correlated significantly with moisture measurement values. Conclusions: Through correlation analysis, the study elucidates the influence of diurnal fluctuations in skin surface lipids on skin barrier function. These findings hold significant implications for understanding skin barrier impairment associated with circadian rhythm disruptions. [ABSTRACT FROM AUTHOR]

Sonoko Harada,1,2 Hitoshi Sasano,1 Shoko Ueda,1 Yuuki Sandhu,1 Sumiko Abe,1 Yuki Tanabe,1 Kyoko Shima,3 Tetsuya Kuwano,3 Yuya Uehara,3 Takayoshi Inoue,3 Ko Okumura,2 Kazuhisa Takahashi,1,4 Norihiro Harada1,2,4 1Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; 2Atopy (Allergy) Research Center, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; 3Biological Science Research, Kao Corporation, Tochigi, Japan; 4Research Institute for Diseases of Old Ages, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, JapanCorrespondence: Norihiro Harada, Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, 3-1-3 hongo, Bunkyo-ku, Tokyo, 113-8431, Japan, Tel +81-3-5802-1063, Fax +81-3-5802-1617, Email nor@juntendo.ac.jpBackground: Examining human coding and non-coding RNAs present in skin surface lipids (SSL-RNAs) offers a promising approach to understanding the physiological state of the skin. Benralizumab treatment can reduce exacerbations and improve symptom control and quality of life in patients with severe eosinophilic asthma. Although this treatment effectively depletes peripheral blood eosinophils, the impact of benralizumab on SSL-RNA remains completely unknown.Objective: To investigate the effects of benralizumab treatment on SSL-RNA profiles in patients with severe asthma.Methods: Skin samples were non-invasively collected from patients before and after one year of benralizumab treatment. Sixteen patients were enrolled, but the SSL-RNA analysis was only feasible for five patients due to collection challenges, mainly in female participants.Results: Following benralizumab treatment, asthma symptoms, exacerbation rates, and lung function parameters improved. Peripheral blood eosinophils were completely depleted and serum eotaxin-1 levels increased. SSL-RNA analysis revealed differential expression of 134 genes, with significant downregulation of immune-related pathways and genes associated with neutrophilic inflammation.Conclusion: These findings suggest a suppression of both type 2 and non-type 2 inflammation in response to benralizumab treatment, with potential implications for asthma management. However, the limitations of the study include a small sample size and challenges in sebum collection, particularly among female participants. Although the noninvasive nature of this sampling method makes it attractive for both research and clinical applications, additional studies are needed to fully investigate the potential of SSL-RNA analysis as a noninvasive biomarker to assess treatment response in asthma.Keywords: asthma, benralizumab, skin surface lipid, sebum, type 2 inflammation

The analysis of skin surface lipid-RNAs (SSL-RNAs) provides a non-invasive method for understanding the molecular pathology of atopic dermatitis (AD), but its relevance to asthma remains uncertain. Although dupilumab, a biologic drug approved for both asthma and AD, has shown efficacy in improving symptoms for both conditions, its impact on SSL-RNAs is unclear. This study aimed to investigate the impact of dupilumab treatment on SSL-RNA profiles in patients with severe asthma. An SSL-RNA analysis was performed before and after administering dupilumab to asthma patients requiring this intervention. Skin samples were collected non-invasively from patients before and after one year of dupilumab treatment. Although 26 patients were enrolled, an SSL-RNA analysis was feasible in only 7 due to collection challenges. After dupilumab treatment, improvements were observed in asthma symptoms, exacerbation rates, and lung function parameters. Serum levels of total IgE and periostin decreased. The SSL-RNA analysis revealed the differential expression of 218 genes, indicating significant down-regulation of immune responses, particularly those associated with type 2 inflammation, suggesting potential improvement in epithelial barrier function. Dupilumab treatment may not only impact type 2 inflammation but also facilitate the normalization of the skin. Further studies are necessary to fully explore the potential of SSL-RNA analysis as a non-invasive biomarker for evaluating treatment response in asthma.

Abstract There have been several reports of skin manifestations in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected on the skin surface, including the sebum, of these patients. In this study, SARS-CoV-2 RNA was detected using real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of skin surface lipids (SSLs) collected using an oil-blotting film from the faces of hospitalized patients with COVID-19. Human transcriptome analysis was also performed using the same samples. In facial SSLs of patients with COVID-19, the RT-PCR positivity rate was 84.6% (11/13 samples) within 5 days and 30.4% (7/23 samples) by 6–10 days of symptom onset. In the transcriptome analysis, the most characteristic SSL-RNA profile was the upregulation of interferon-stimulated gene (ISG)-related genes, such as ISG15, IFITM1, and MX1. This study presents an alternative technique using SSLs for non-invasive SARS-CoV-2 RNA detection and simultaneous analysis of human molecular pathogenesis in patients with COVID-19.

Background: Intense pulsed light (IPL) has been widely used to improve cutaneous photoaging in recent years. Several studies began to explore the changes of skin barrier function after treatment, but the changes of skin surface lipids (SSL), especially specific lipid content and types are still unclear. Methods: A total of 25 female volunteers were included in our study, and each of them received three full-face treatments with one month apart. Before the first treatment and 1 month after the last treatment, we collected clinical photos and skin stratum corneum samples from individuals. A 5-level scale was used to evaluate the efficacy of IPL treatment, liquid chromatography-mass spectrometry (LC-MS), and Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA) were used to analyze the changes of SSL. Results: Two patients got no improvement after treatment, 6 patients had poor improvement and mild improvement was achieved in 9 patients, 5 and 3 patients reported moderate and significant improvement. The overall "effective" rate was 68 % and the "significant effective" rate was 32 %. The results showed 18 lipid subclasses and 487 lipid molecules were identified. The change of total lipid volume was not statistically significant (P = 0.088>0.05), but lipid subclass analysis showed the amount of Triglyceride (TG), Phosphatidic Acid (PA), Phosphatidylglycerol (PG) and Lysophosphatidylglycerol (LPG) were significantly increased (P < 0.05). There were 55 kinds of lipid molecules with significant difference after treatment (P < 0.05), and 51 of them belong to TG. The analysis of chain saturation of TG showed that the quantity of TG with 0, 1 and 2 unsaturated bonds increased significantly (P < 0.05). Conclusions: IPL treatment does not have a significant effect on the overall amount of lipids while the amount of TG, PA, PG, LPG were significantly increased. These lipid changes may potentially improve the skin barrier function, but more high-quality and comprehensive studies are still needed. Bullet Point: Lipidomics analysis based on LC-MS; Changes of skin surface lipid after IPL treatment; the relationships between skin surface lipid and skin barrier functions. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background and Aims: Self‐perception of sensitive skin (SPSS) has several consequences, including skin barrier damage, which is prevented by barrier sebum. We analyzed lipidome profiles of skin surface lipids (SSLs) in patients with SPSS and healthy controls and explored the mechanism of action of potential lipid markers on the repair of damaged barrier cells to better understand SSL abnormity in these patients. Methods: Ultraperformance liquid chromatography–quadrupole time‐of‐flight mass spectrometry was used to investigate SSL variations in major lipid classes, subclasses, and species. Reverse‐transcription polymerase chain reaction (RT‐PCR) was used to examine changes in intracellular gene expression following cell barrier damage repair by potential lipid markers. Results: There were significant differences in the lipidomes of individuals between groups. Individuals with SPSS showed significantly increased levels of two diacylglycerols and one very‐short‐chain free fatty acid and significantly decreased levels of three ceramides (Cers), four glycerophospholipids, and one very‐long‐chain free fatty acid. RT‐PCR revealed that after damage repair by Cer/Glucosylceramide (GlcCer), the expression of two genes in the sterol regulatory element‐binding protein and three in the peroxisome proliferator‐activated receptor pathway significantly increased. Causes of skin barrier damage in patients with SPSS are related to the amount and type of lipids. Conclusion: Cer/GlcCer can promote lipid synthesis and secretion by upregulating lipid‐related gene expression to repair barrier damage. [ABSTRACT FROM AUTHOR]

The skin barrier of melasma is involved in the pathogenesis of melasma. Previous studies have shown that there are differences in the expression of epidermal lipid genes in melasma, but little is known about the epidermis lipid composition of melasma. Compared with the non‐lesional skin, the content of total lipids, phosphatidic acid, phosphatidylserine, and ceramide (Cer) increased significantly in the lesional skin. Multivariate data analysis indicated that 40 individual Cer lipid species were responsible for the discrimination. In terms of acyl chain length in Cer, the expressions of very long chain (VLC) (C20–C26) and ultra‐long chain (ULC) (>C26) increased significantly in the lesional skin. However, Cer[AH] had negative correlations with the activation of melanocytes in the lesional skin. Some lipid species had lower expression in lesional skin with high activation of melanocytes, as well as the high darkness. The epidermal thickness of lesional skin was higher compared with the non‐lesional skin. These results suggest that Cer increased significantly in the lesional skin of melasma, possibly as a compensatory mechanism to maintain skin barrier function. Between different groups of darkness and activation of melanocytes, the change of ceramides might have correlation with the pigmentation progress of melasma. [ABSTRACT FROM AUTHOR]

Background: Infantile acne refers to a skin disease that usually occurs on the face from 6 weeks to 1 year old, and the etiology of infantile acne is different from that of puberty acne. The change of skin surface lipid (SSL) is an important factor in the occurrence of acne. Objectives: Comparison of facial skin lipid changes in healthy and acne‐prone infants, screening for possible groupings of substances, to explore factors associated with the development of acne in infants, such as gender and frequency of face washing. Methods: A questionnaire was used to obtain information about the infant, facial lipids were affixed with adhesive tape, and the samples were analyzed using Ultraperformance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UPLC‐QTOF‐MS), with subsequent data analyzed by single‐factor and multifactor analysis. Results: It was observed that some lipids followed the trend of lipid master classes, subclasses and were significantly different. Galactosylceramides, glycosylceramides and phosphatidylethanolamine were screened as the majority of differentiating lipid species. Additionally, it was emphasized that the frequency of face washing and parent's acne was independent with the severity of acne in infant by clinical characteristics, whereas the skin type and gender can affect the severity of acne statistically. Conclusions: Facial lipids change significantly between infantile acne and healthy infants, suggesting that qualitative and quantitative changes in lipids are strongly associated with the development of acne and may exacerbate the environment in which acne occurs. [ABSTRACT FROM AUTHOR]

Background: Pregnancy is a complex physiological state and its unique changes in skin state have been discussed. Skin surface lipid (SSL) is an important molecular basis for this skin condition, and it affects skin condition in a number of ways, but there are no complete research data on it. Objectives: To analyze the lipidome profiles of SSL in pregnancies and controls in order to understand SSL changes in pregnancy. It will provide theoretical data of SSL on skin care and prevention of skin diseases during pregnancy. Methods: Ultra‐high performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (UPLC‐QTOF‐MS) and multivariate statistics were used to investigate the changes of SSL in pregnancy. Results: Results showed that there were significant differences (P <.05) in the lipidome between pregnancies and controls. Multivariate data analysis indicated that there were 20 important individual lipid species identified, and triglycerides (TGs) were the majority of differentiating lipid species. Conclusions: The increase of estrogen level in pregnancies antagonizes and inhibits the regulation of androgen on sebaceous gland, resulting in the decrease of sebum secretion and the weakening of skin barrier function. Besides, the decrease of saturated fatty acid content may be the main factor of the decrease of skin barrier function during pregnancy. Additionally, skin cells perform their self‐regulation function to reduce or counteract abnormal state of the skin during pregnancy through the synthesis and secretion of more glycerophospholipids and ceramides. [ABSTRACT FROM AUTHOR]

Background: Fatty acids are common raw materials in cosmetics and also are an important component of skin surface lipids, and their composition and amount affect the skin condition. Aims: The purpose of this article was to review the results of basic research on fatty acids as skin surface lipids. Methods: An extensive literature search was conducted using PubMed, Web of Science, and other databases for articles on fatty acids from 1993 to 2020. Results: This article provides an overview of the mechanisms of fatty acid synthesis and its metabolic pathways as skin surface lipids in the context of sebaceous and intercellular lipids. The three mechanisms by which fatty acids affect the skin condition are also reviewed. Conclusions: This information will aid further understanding of the mechanism of the fatty acid role in skin function maintenance and provide new perspectives for the management of skin health. [ABSTRACT FROM AUTHOR]

Background: Regional differences in skin characteristics are well known. Significant differences in skin physiology between the forehead and cheek have also been reported. However, there are few studies based on lipidomics at the molecular level. Additionally, there is no study focusing on the lipid profile variations of skin surface lipid (SSL) in forehead and cheek. Purpose: This study analyzed the differences in facial SSL between forehead and cheek of men aged 18‐25 years to explain the distinct physiological parameters between forehead and cheek resulting in different skin status. Methods: Facial SSL was identified by ultra‐performance liquid chromatography‐quadrupole time of flight‐mass spectrometry (UPLC‐QTOF‐MS). Multivariate data analysis was used to investigate the SSL difference in forehead and cheek. Results: Significant differences in facial SSL composition were detected between the forehead and cheek. Multivariate data analysis suggested that 21 entities contributed most significantly toward the discrimination and phosphatidylserines (PS) constituted the majority of differentiating lipid species. Subsequent analysis showed a marked increase in the amounts of unsaturated and saturated free fatty acids (FFAs), and a significant increase in average FFAs chain length in the forehead as compared to that in the cheek. Conclusions: Phosphatidylserines exposure might be one of the most important reasons for the increased amount of forehead SSL secretion. The different FFAs chain length and FFAs content lead to altered skin barrier functions in forehead and cheek, consequently resulting in altered trans‐epidermal water loss (TEWL) and pH at the two anatomical sites. [ABSTRACT FROM AUTHOR]

Background: The circadian rhythm is an endogenous clock that governs a wide range of physiological functions. In the skin, rhythmic changes in skin barrier function have been investigated at the physiological level; however, few studies at the molecular level have been reported. Additionally, there is no study on lipidomic profile variations of skin surface lipid (SSL), which could potentially explain the rhythmic changes in skin status. Objectives: The SSL profile of healthy young women was analysed to assess SSL variations and to assess the skin status during the circadian cycle. Methods: Ultra performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry and multivariate data analysis were performed to assess SSL variations. Results: The lipidomic profile showed significant differences with the circadian rhythm. Multivariate data analysis indicated that glycerolipids were the lipids majorly affected by the circadian rhythm. Additionally, in the SSL profile, both the average chain length and the content of free fatty acids (FFAs) were higher at 20:00 than at 08:00. Conclusions: The SSL profile significantly varied with respect to the circadian rhythm. The rhythm‐altered triacylglycerol level, FFA chain length and FFA content resulted in rhythmic changes in skin barrier function, including transepidermal water loss alteration and pH variation. [ABSTRACT FROM AUTHOR]

Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with reasonable amounts found in olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main component of skin surface polyunsaturated lipids, shows some advantages for the skin as an emollient and antioxidant, and for hydration and its antitumor activities. It is also used as a material in topically applied vehicles such as lipid emulsions and nanostructured lipid carriers (NLCs). Substances related to squalene, including β-carotene, coenzyme Q10 (ubiquinone) and vitamins A, E, and K, are also included in this review article to introduce their benefits to skin physiology. We summarize investigations performed in previous reports from both in vitro and in vivo models.

Background: Human health status can be measured on the basis of many different parameters. Statistical relationships among these different health parameters will enable several possible health care applications and an approximation of the current health status of individuals, which will allow for more personalized and preventive health care by informing the potential risks and developing personalized interventions. Furthermore, a better understanding of the modifiable risk factors related to lifestyle, diet, and physical activity will facilitate the design of optimal treatment approaches for individuals., Objective: This study aims to provide a high-dimensional, cross-sectional data set of comprehensive health care information to construct a combined statistical model as a single joint probability distribution and enable further studies on individual relationships among the multidimensional data obtained., Methods: In this cross-sectional observational study, data were collected from a population of 1000 adult men and women (aged ≥20 years) matching the age ratio of the typical adult Japanese population. Data include biochemical and metabolic profiles from blood, urine, saliva, and oral glucose tolerance tests; bacterial profiles from feces, facial skin, scalp skin, and saliva; messenger RNA, proteome, and metabolite analyses of facial and scalp skin surface lipids; lifestyle surveys and questionnaires; physical, motor, cognitive, and vascular function analyses; alopecia analysis; and comprehensive analyses of body odor components. Statistical analyses will be performed in 2 modes: one to train a joint probability distribution by combining a commercially available health care data set containing large amounts of relatively low-dimensional data with the cross-sectional data set described in this paper and another to individually investigate the relationships among the variables obtained in this study., Results: Recruitment for this study started in October 2021 and ended in February 2022, with a total of 997 participants enrolled. The collected data will be used to build a joint probability distribution called a Virtual Human Generative Model. Both the model and the collected data are expected to provide information on the relationships between various health statuses., Conclusions: As different degrees of health status correlations are expected to differentially affect individual health status, this study will contribute to the development of empirically justified interventions based on the population., International Registered Report Identifier (irrid): DERR1-10.2196/47024., (©Masanobu Hibi, Shun Katada, Aya Kawakami, Kotatsu Bito, Mayumi Ohtsuka, Kei Sugitani, Adeline Muliandi, Nami Yamanaka, Takahiro Hasumura, Yasutoshi Ando, Takashi Fushimi, Teruhisa Fujimatsu, Tomoki Akatsu, Sawako Kawano, Ren Kimura, Shigeki Tsuchiya, Yuuki Yamamoto, Mai Haneoka, Ken Kushida, Tomoki Hideshima, Eri Shimizu, Jumpei Suzuki, Aya Kirino, Hisashi Tsujimura, Shun Nakamura, Takashi Sakamoto, Yuki Tazoe, Masayuki Yabuki, Shinobu Nagase, Tamaki Hirano, Reiko Fukuda, Yukari Yamashiro, Yoshinao Nagashima, Nobutoshi Ojima, Motoki Sudo, Naoki Oya, Yoshihiko Minegishi, Koichi Misawa, Nontawat Charoenphakdee, Zhengyan Gao, Kohei Hayashi, Kenta Oono, Yohei Sugawara, Shoichiro Yamaguchi, Takahiro Ono, Hiroshi Maruyama. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.06.2023.)