mRNAs in skin surface lipids unveiled atopic dermatitis at 1 month.

BACKGROUND: The molecular pathogenesis of atopic dermatitis (AD), presenting skin barrier dysfunction and abnormal inflammations around 1-2 months, is unreported. OBJECTIVE: We aimed to examine the molecular pathogenesis of very early-onset AD by skin surface lipid-RNA (SSL-RNA) using a non-invasive technology in infants aged 1 and 2 months from a prospective cohort. METHODS: We collected sebum by oil-blotting film of infants aged 1 and 2 months and analysed RNAs in their sebum. We diagnosed AD according to the United Kingdom Working Party's criteria. RESULTS: Infants with AD aged 1 month showed lower expression of genes related to various lipid metabolism and synthesis, antimicrobial peptides, tight junctions, desmosomes and keratinization. They also had higher expression of several genes involved in Th2-, Th17- and Th22-type immune responses and lower expression of negative regulators of inflammation. In addition, gene expressions related to innate immunity were higher in AD infants. Infants aged 1 month with neonatal acne and diagnosed with AD aged 2 months already had gene expression patterns similar to AD aged 1 month in terms of redox, lipid synthesis, metabolism and barrier-related gene expression. CONCLUSION: We identified molecular changes in barrier function and inflammatory markers that characterize the pathophysiology of AD in infants aged 1 month. We also revealed that neonatal acne at 1 month could predict the subsequent development of AD by sebum transcriptome data.

Carbon dioxide inhibits UVB-induced inflammatory response by activating the proton-sensing receptor, GPR65, in human keratinocytes.

Carbon dioxide (CO2) is the predominant gas molecule emitted during aerobic respiration. Although CO2 can improve blood circulation in the skin via its vasodilatory effects, its effects on skin inflammation remain unclear. The present study aimed to examine the anti-inflammatory effects of CO2 in human keratinocytes and skin. Keratinocytes were cultured under 15% CO2, irradiated with ultraviolet B (UVB), and their inflammatory cytokine production was analyzed. Using multiphoton laser microscopy, the effect of CO2 on pH was observed by loading a three-dimensional (3D)-cultured epidermis with a high-CO2 concentration formulation. Finally, the effect of CO2 on UVB-induced erythema was confirmed. CO2 suppressed the UVB-induced production of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in keratinocytes and the 3D epidermis. Correcting medium acidification with NaOH inhibited the CO2-induced suppression of TNFα and IL-6 expression in keratinocytes. Moreover, the knockdown of H+-sensing G protein-coupled receptor 65 inhibited the CO2-induced suppression of inflammatory cytokine expression and NF-κB activation and reduced CO2-induced cyclic adenosine monophosphate production. Furthermore, the high-CO2 concentration formulation suppressed UVB-induced erythema in human skin. Hence, CO2 suppresses skin inflammation and can be employed as a potential therapeutic agent in restoring skin immune homeostasis.

Carbon dioxide ameliorates reduced desquamation in dry scaly skin via protease activation.

OBJECTIVE: Scaling, a phenomenon showing an abnormal detachment of the stratum corneum (SC) owing to desquamation dysfunction, is commonly observed in various skin diseases or xerotic skin due to ageing and low humidity. Therefore, it is considered that ameliorating the disturbed desquamatory process of the SC leads to improvement in scaling. Carbon dioxide (CO2 ) is known to be good for some skin diseases; however, the effect of CO2 on scaling and its mechanism are not sufficiently clear. We aimed to elucidate the effect of transepidermal application of CO2 on scaling and its mechanism of action. METHODS: Twenty healthy men with mild scaling on the cheeks were recruited for a double-blind, placebo-controlled, split-face study. They applied the formulation containing CO2 twice daily for 1 week. After the study, the SC was collected by tape stripping to analyse desquamatory protease activities and degradation of extracellular corneodesmosomes. Furthermore, the contribution of pH to proteolysis of the corneodesmosome by CO2 was evaluated using three-dimensional (3D) cultured epidermal models. RESULTS: The spectroscopic absorbance of tape strips, used as scaling indicators, was decreased, concomitantly with the amelioration of incomplete degradation of desmoglein-1, one of the main corneodesmosomal proteins, and activation of trypsin-like protease in the SC by transepidermal application of CO2 . Experiments using 3D cultured epidermis showed that pH in the epidermal tissue was lowered by CO2 , whereas a pH change was not observed with the application of the formulation containing hydrochloric acid, which was added to equalize the pH to that of the CO2 formulation. CONCLUSION: The transcutaneous application of CO2 ameliorates reduced desquamatory process in xerotic skin, with concomitant mild acidification of the SC, thereby leading to improvement in scaling. Thus, CO2 may have an advantage of efficiently and safely counteracting scaling of various skin disorders.

OBJECTIF: La desquamation, phénomène caractérisé par un détachement anormal de la couche cornée (CC) dû à un dysfonctionnement de l'épiderme, est fréquemment observée dans diverses maladies de la peau ou en cas de xérose résultant du vieillissement et de la faible humidité. Par conséquent, il est considéré que le soulagement du trouble à l'origine du processus desquamant de la CC réduit la desquamation. Le dioxyde de carbone (CO2) est réputé bénéfique pour certaines maladies de la peau. Cependant, l'effet du CO2 sur la desquamation et son mécanisme ne sont pas suffisamment clairs. Nous avons cherché à élucider l'effet de l'application transépidermique du CO2 sur la desquamation et son mécanisme d'action. MÉTHODES: Vingt hommes en bonne santé, présentant une légère desquamation sur les joues, ont été recrutés dans le cadre d'une étude en double aveugle, contrôlée par un placebo, en hémiface. Ils ont appliqué la formule contenant du CO2 deux fois par jour, pendant 1 semaine. Après l'étude, la CC a été recueillie par décollement de ruban adhésif, en vue de l'analyse des activités de la protéase desquamante et de la dégradation des cornéodesmosomes extracellulaires. En outre, la contribution du pH à la protéolyse du cornéodesmosome par le CO2 , a été évaluée à l'aide de modèles d'épidermes cultivés tridimensionnels (3D). RÉSULTATS: L'absorbance spectroscopique des bandelettes de ruban adhésif, utilisées comme indicateurs de desquamation, a été réduite, concomitamment avec la baisse de la dégradation incomplète de la desmogléine-1, l'une des principales protéines des cornéodesmosomes, et l'activation de la trypsine dans la CC par application transépidermique de CO2 . Des expériences menées sur un épiderme cultivé en 3D ont montré que le pH dans le tissu épidermique était réduit par le CO2 , tandis qu'aucun changement de pH n'a été observé avec l'application de la formule contenant de l'acide chlorhydrique, ajoutée pour que le pH soit identique à celui de la formule contenant du CO2 . CONCLUSION: L'application transcutanée de CO2 améliore la réduction du processus desquamant de la peau atteinte de xérose, avec une légère acidification concomitante de la CC, entraînant ainsi une réduction de la desquamation. Par conséquent, le CO2 peut présenter l'avantage de contrer la desquamation de manière efficace et sûre, pour diverses affections cutanées.

Coffee polyphenols extracted from green coffee beans improve skin properties and microcirculatory function.

Coffee polyphenols (CPPs), including chlorogenic acid, exert various physiological activities. The purpose of this study was to investigate the effects of CPPs on skin properties and microcirculatory function in humans. In this double-blind, placebo-controlled study, 49 female subjects with mildly xerotic skin received either a test beverage containing CPPs (270 mg/100 mL/day) or a placebo beverage for 8 weeks. The ingestion of CPPs significantly lowered the clinical scores for skin dryness, decreased transepidermal water loss, skin surface pH, and increased stratum corneum hydration and the responsiveness of skin blood flow during local warming. Moreover, the amounts of free fatty acids and lactic acid in the stratum corneum significantly increased after the ingestion of CPPs. These results suggest that an 8-week intake of CPPs improve skin permeability barrier function and hydration, with a concomitant improvement in microcirculatory function, leading to efficacy in the alleviation of mildly xerotic skin.

Gene cloning and deletion analysis of chitinase J from alkaliphilic Bacillus sp. strain J813.

Alkaliphilic Bacillus sp. strain J813 produces a novel chitinase (chitinase J). The gene encoding chitinase J (chij) was cloned and sequenced. Deduced amino acid sequence revealed that Chij contained a family 18 catalytic domain, a fibronectin type III-like domain and a chitin-binding domain. Analysis of deletion derivatives indicated that the chitin-binding domain was important for binding to chitin and it enhanced the hydrolysis of insoluble chitin. The subsites existing in the catalytic domain of Chij was thought to bind to insoluble chitosan, although Chij did not hydrolyze chitosan. Some amino acid-substituted mutants were prepared and characterized, suggesting that Glu198 should be the catalytic residue of Chij.