Rosmarinic acid ameliorates HCl-induced cystitis in rats.

Shiso (Perilla frutescens var crispa f. purprea) is a traditional medicinal herb that exerts anti-inflammatory effects and alleviates lower urinary tract symptoms. In this study, we examined the effects of rosmarinic acid, a major polyphenol in shiso, on urinary function and the bladder in a rat hydrochloric acid-induced cystitis model. Sprague-Dawley rats were administered intravesically with hydrochloric acid or saline solution (control) to induce cystitis. Afterwards, the rats were administered orally with distilled water or rosmarinic acid for three days and then the intravesical pressure was measured, a stretch stimulation test was performed using the harvested bladder, and histological and biochemical analyses were performed. In addition, we investigated the effects of rosmarinic acid on the expression of inflammation-related molecules in normal human bladder epithelial cells. Rosmarinic acid ameliorated hydrochloric acid-induced shortening of micturition interval by 49%. In hydrochloric acid-treated bladders, significantly more prostaglandin E2 was released after stretching; however, rosmarinic acid suppressed its release to control levels. Rosmarinic acid also reduced hydrochloric acid-induced epithelial thickening and the levels of inflammatory molecules in the bladder. Furthermore, rosmarinic acid suppressed interleukin 1ß-induced increases in Cox2 and Il6 expression in bladder epithelial cells. These findings indicate that rosmarinic acid can ameliorate hydrochloric acid-induced cystitis in rats and that these effects are due, at least in part, to its anti-inflammatory effects on the bladder and inhibition of stretch-induced prostaglandin E2 release.

Oleic acid-induced interleukin-36γ: A possible link between facial skin redness and sebum.

BACKGROUND: Redness of the facial skin is an important cosmetic concern. Although qualitative and quantitative modifications of sebum on the skin surface are major pathogenic factors of chronic inflammatory skin conditions, the relationship between skin redness, sebum, and mild inflammation on the cheeks of healthy subjects remains elusive. AIMS: We aimed to explore the correlation between cheek redness and sebum and inflammatory cytokines in the stratum corneum (SC) of healthy subjects. We also examined the effects of representative sebum lipids on the gene expression of inflammatory cytokines in cultured keratinocytes. PATIENTS/METHODS: This study included 198 healthy participants. Skin sebum was analyzed using flow injection analysis, and skin redness was assessed using a spectrophotometer. Inflammatory cytokines in tape-stripped SC were measured using enzyme-linked immunosorbent assay. RESULTS: Cheek redness parameters positively correlated with the amount of skin sebum and the proportion of monounsaturated free fatty acids (C16:1 and C18:1) in the sebum. They also positively correlated with the interleukin (IL)-36γ/IL-37 ratio in the SC. Among the representative sebum lipids examined, oleic acid (C18:1, cis-9) dose- and time-dependently regulated the mRNA expression of IL-36γ and IL-37 in cultured keratinocytes, and this effect was attenuated by the N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist, MK801. CONCLUSIONS: Skin surface sebum may be related to cheek redness in healthy subjects, and oleic acid-induced IL-36γ through NMDA-type glutamate receptors may be a link between them. Our study provides a possible skincare strategy for mitigating unfavorable increase in skin redness by targeting the facial skin sebum, particularly oleic acid.

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.

Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids.

Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed increased expression of inflammation-related genes and decreased expression of terminal differentiation-related genes, consistent with the results of previous reports. Further, we found that lipid synthesis-related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

Non-invasive evaluation of subjective sensitive skin by transcriptomics using mRNA in skin surface lipids.

Sensitive skin is a condition characterized by hypersensitivity to environmental stimuli, and its pathophysiology has not been fully elucidated. Questionnaires based on subjective symptoms, intervention tests, and measuring devices are used to diagnose sensitive skin; however, objective evaluation methods, including biomarkers, remain to be established. This study aimed to investigate the molecular profiles of self-reported sensitive skin, understand its pathophysiology and explore its biomarkers. Here, we analysed RNAs in skin surface lipids (SSL-RNAs), which can be obtained non-invasively by wiping the skin surface with an oil-blotting film, to compare the transcriptome profiles between questionnaire-based "sensitive" (n = 11) and "non-sensitive" (n = 10) skin participants. Exactly 417 differentially expressed genes in SSL-RNAs from individuals with sensitive skin were identified, of which C-C motif chemokine ligand 17 and interferon-γ pathways were elevated, while 50 olfactory receptor (OR) genes were downregulated. The expression of the detectable 101 OR genes was lower in individuals with sensitive skin compared to that in those with non-sensitive skin and was particularly associated with the subjective sensitivity among skin conditions. The receiver operating characteristic (ROC) curve demonstrated that the mean expression levels of OR genes in SSL-RNAs could discriminate subjective skin sensitivity with an area under the ROC curve of 0.836. SSL-RNA profiles suggest a mild inflammatory state in sensitive skin, and overall OR gene expression could be a potential indicator for sensitive skin.

Non-invasive diagnostic tool for Parkinson's disease by sebum RNA profile with machine learning.

Parkinson's disease (PD) is a progressive neurodegenerative disease presenting with motor and non-motor symptoms, including skin disorders (seborrheic dermatitis, bullous pemphigoid, and rosacea), skin pathological changes (decreased nerve endings and alpha-synuclein deposition), and metabolic changes of sebum. Recently, a transcriptome method using RNA in skin surface lipids (SSL-RNAs) which can be obtained non-invasively with an oil-blotting film was reported as a novel analytic method of sebum. Here we report transcriptome analyses using SSL-RNAs and the potential of these expression profiles with machine learning as diagnostic biomarkers for PD in double cohorts (PD [n = 15, 50], controls [n = 15, 50]). Differential expression analysis between the patients with PD and healthy controls identified more than 100 differentially expressed genes in the two cohorts. In each cohort, several genes related to oxidative phosphorylation were upregulated, and gene ontology analysis using differentially expressed genes revealed functional processes associated with PD. Furthermore, machine learning using the expression information obtained from the SSL-RNAs was able to efficiently discriminate patients with PD from healthy controls, with an area under the receiver operating characteristic curve of 0.806. This non-invasive gene expression profile of SSL-RNAs may contribute to early PD diagnosis based on the neurodegeneration background.

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.

The ceramide [NP]/[NS] ratio in the stratum corneum is a potential marker for skin properties and epidermal differentiation.

BACKGROUND: Specific species of ceramides (Cer), major constituents of lipids in the stratum corneum (SC), are decreased and are correlated with SC barrier and water-holding functions in the skin of patients with atopic dermatitis (AD) or psoriasis (Pso). However, possible correlations between Cer subclass ratios and skin properties in barrier-disrupted skin and in healthy skin remain unclear. The objective of this study was to identify a new marker to evaluate skin properties and epidermal differentiation in SC not only in barrier-disrupted skin but also in healthy skin. METHODS: The Cer subclass ratios in the SC of healthy control subjects and in patients with AD or Pso were evaluated. Correlations with candidate markers and facial skin features of healthy Japanese females (20-74 years old, n = 210) were investigated. Variations of markers during epidermal differentiation were studied in human epidermis and in cultured keratinocytes. RESULTS: The ratios of Cer [NP]/[NS], Cer [NH]/[NS], Cer [NP]/[AS], Cer [NH]/[NS], Cer [NDS]/[AS], Cer [AH]/[AS] and Cer [EOP]/[AS] showed significant differences between non-lesional skin of AD patients and normal skin of healthy control subjects, as well as Pso patients and their healthy control subjects. The Cer [NP]/[NS] ratio was correlated with SC functional parameters (transepidermal water loss and capacitance) and with skin appearance (texture, scaling and color) even in the cheek skin of healthy female subjects. The Cer [NP]/[NS] ratio in the SC was approximately 18-times higher than in living keratinocytes, and it increased as they differentiated. CONCLUSIONS: The Cer [NP]/[NS] ratio in the SC is a potential marker for skin properties and epidermal differentiation in barrier-disrupted skin as well as in healthy skin.

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.

Obesity-associated insulin resistance adversely affects skin function.

The aim of this study was to identify changes in skin function associated with obesity and the mechanisms underlying these changes. Functional changes and gene expression in skin were investigated in C57BL/6J mice fed either a control or high-fat diet (HFD). The insulin responsiveness of the skin and skeletal muscle was also evaluated. The effects of inhibiting insulin signaling and altered glucose concentration on skin function-associated molecules and barrier function were analyzed in keratinocytes. HFD-fed mice were not only severely obese, but also exhibited impaired skin barrier function and diminished levels of glycerol transporter aquaporin-3, keratins, and desmosomal proteins involved in maintaining skin structure. Moreover, the expression of cell cycle regulatory molecules was altered. Insulin signaling was attenuated in the skin and skeletal muscle of HFD-fed mice. In keratinocytes, inhibition of insulin signaling leads to decreased keratin expression and diminished barrier function, and higher glucose concentrations increased the expression of CDK inhibitor 1A and 1C, which are associated with cell-cycle arrest. Obesity-associated impairment of skin function can be attributed to structural fragility, abnormal glycerol transport, and dysregulated proliferation of epidermal cells. These alterations are at least partly due to cutaneous insulin resistance and hyperglycemia.

Synergistic activation of thermogenic adipocytes by a combination of PPARγ activation, SMAD3 inhibition and adrenergic receptor activation ameliorates metabolic abnormalities in rodents.

AIMS/HYPOTHESIS: To treat obesity and related diseases, considerable effort has gone into developing strategies to convert white adipocytes into thermogenic brown-like adipocytes ('browning'). The purpose of this study was to identify the most efficient signal control for browning. METHODS: To identify the most efficient signal control for browning, we examined rat stromal vascular fraction cells. In addition, physiological changes consequent to signal control were examined in vivo using lean and diet-induced obese (DIO) C57BL/6J mice. RESULTS: Combined treatment with the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone, the SMAD3 inhibitor SIS3 and the adrenergic receptor agonist noradrenaline (norepinephrine) synergistically induced Ucp1, Fgf21 and Cited1 expression, triggering brown adipogenesis. Synergistic induction of Ucp1 by the three agents was negatively regulated by forkhead box O (FOXO)3 via the inhibition of PPARγ-dependent gene transcription. Moreover, the administration of rosiglitazone, SIS3 and the selective ß3 adrenergic receptor agonist CL316,243 to DIO mice reduced the amount of body-fat deposits (body weight from day 0 to 14, 12.3% reduction), concomitant with morphological changes in white adipose tissue, an increase in mitochondrial biosynthesis and a marked induction of uncoupling protein 1 (UCP1). Furthermore, administration of the three agents significantly increased serum adiponectin levels (mean 65.56 µg/ml with the three agents vs 20.79 µg/ml in control mice, p < 0.05) and improved glucose and lipid tolerance. CONCLUSIONS/INTERPRETATION: These results suggest that the combined regulation of PPARγ, SMAD and the adrenergic receptor signalling pathway synergistically induces brown adipogenesis and may serve as an effective strategy to treat obesity and related diseases, including type 2 diabetes.

Facial application of high-concentration carbon dioxide prevents epidermal impairment associated with environmental changes.

PURPOSE: The transdermal application of carbon dioxide (CO2) gas dissolved in a solution and bathing in carbonated springs have been known to improve circulatory disorders. We aimed to elucidate and profile the effects of CO2 application on local skin function. PATIENTS AND METHODS: A liquid formulation that included high-concentration CO2 or a control formulation was applied to the face of healthy men for 8 weeks. Quantitative analysis was performed during the dry winter months. RESULTS: At the site where the control formulation was applied, transepidermal water loss (TEWL) increased while the moisturizing function (conductance) of facial skin decreased during the study period. However, at the CO2-treated site, increases in TEWL and decreases in conductance were significantly suppressed. In addition, the deterioration in scaliness and wrinkles parameters were suppressed by ≥40% at the CO2-treated site. There were no significant differences in skin surface pH or color properties between the control and test sites. CONCLUSION: This study suggests that the continuous application of a high-concentration CO2 formulation can affect skin physiology and has the potential to suppress reductions in the barrier and moisturizing functions of the stratum corneum accompanied by desquamation, which occurs during the winter.

Ingestion of coffee polyphenols suppresses deterioration of skin barrier function after barrier disruption, concomitant with the modulation of autonomic nervous system activity in healthy subjects.

The aim of this study was to evaluate the effect of consumption of coffee polyphenols (CPPs) on the autonomic nervous system activity and decreased skin barrier function caused by sodium dodecyl sulfate (SDS) treatment. In this single-blind, placebo-controlled study, ten healthy male subjects consumed either a beverage containing CPPs or a placebo beverage for four weeks. CPPs significantly suppressed the deterioration in skin barrier function and skin moisture content induced by SDS treatment after the third week. Furthermore, in the heart rate variability analysis, CPPs significantly produced an increase in parasympathetic nervous activity, and a decrease in sympathetic nervous activity after the four weeks of beverage consumption. These results suggest that CPPs might influence the regulation of the autonomic nervous system and contribute to the suppressive effect on deterioration of skin barrier function.

Dietary intake of glucono-δ-lactone attenuates skin inflammation and contributes to maintaining skin condition.

Skin properties are influenced by both external (e.g., ultraviolet [UV], chemicals, and bacteria) and internal factors (e.g., nutrition and hormones). Therefore, some dietary supplements are expected to improve skin conditions. Glucono-δ-lactone (GDL) is widely used as a food additive and is naturally present in wine, honey, and other foods. The aim of this study was to assess whether GDL improves skin condition and inflammation. In a double-blind, placebo-controlled study, 40 healthy Japanese male volunteers were randomly assigned to either the GDL (2000 mg day-1) or placebo group. A significant difference was found in the rates of change in transepidermal water loss (TEWL) from the baseline to 6 months between the placebo and GDL groups (P < 0.05). Facial lightness (L*) significantly increased by 1.6% only in the GDL group at 6 months compared with the baseline. The value of the elasticity parameter, Ua/Uf, of dietary GDL significantly increased (6.2% at 2 months and 5.4% at 6 months). Besides these, dietary GDL suppressed UVB-induced erythema (a*) and pigmentation (L*). Dietary GDL has anti-inflammatory effects on the skin and prevents/improves skin disorders caused by seasonal change.

Perilla extract improves frequent urination in spontaneously hypertensive rats with enhancement of the urothelial presence and anti-inflammatory effects.

OBJECTIVE: To investigate the effects of perilla extract on urinary symptoms in spontaneously hypertensive rats as a model of spontaneous overactive bladder. METHODS: Spontaneously hypertensive rats were randomly divided into two groups and fed either a control diet or a perilla extract-containing diet. Cystometry, gene expression and histological analyses were carried out to evaluate the effects of perilla extract after 2-week feeding of either the control or the perilla extract diet. The expression of inflammation-related genes in the human urothelial cell line HT-1376 and the normal human bladder epithelial cell was measured after the treatment with perillaldehyde, the main component of perilla extract, or perillic acid, the final metabolite of perillaldehyde. RESULTS: A significant 27% increase in the micturition interval and decreased expression of nerve growth factor, tumor necrosis factor-α, interleukin-1ß and transient receptor potential V1 were observed in the perilla group compared with the control group. The level of uroplakin 3A was 40% higher in the perilla group than in the control group. The urothelium in the control group was thin or defective, but it was almost completely intact in the perilla group. Perillaldehyde and perillic acid suppressed the induction of nerve growth factor and tumor necrosis factor-α by interleukin-1ß in HT-1376 and normal human bladder epithelial cells. CONCLUSIONS: The present findings suggest that perilla extract improves frequent urination, and this improvement seems to be mediated, at least in part, by enhancement of the urothelial presence and by the anti-inflammatory effects of perilla.

Correction to: Characterization of skin function associated with obesity and specific correlation to local/systemic parameters in American women.

Following publication of the original article [1], the authors identified an error. In the description in Fig. 1b the "solid line" "dashed line" should be exchanged. The original article has been updated.

Characterization of skin function associated with obesity and specific correlation to local/systemic parameters in American women.

BACKGROUND: Obesity is considered problematic not only as a major cause of diabetes, hypertension, and dyslipidemia, but also as a risk of intractable dermatosis; however influence of obesity on skin function has not been clarified. To clarify the mechanism of obesity-associated skin disorders, we aimed to characterize the skin function of subjects with obesity, and identify possible influencing factors. METHODS: Complex analyses including instrumental measurement, biochemical and lipidomics were performed for facial skin and physical evaluation in 93 Caucasian women with obesity (OB) and non-obesity (NOB). RESULTS: In OB, imbalance in metabolism of carbohydrate and lipid, autonomic nerve activity, and secreted factors were confirmed. In the skin properties in OB, surface roughness was higher by 70%, the water content was lower by 12%, and changes in the lipid profile of stratum corneum ceramide were observed; in particular, a 7% reduction of [NP]-type ceramide, compared with NOB. Moreover, significant redness accompanied by a 34% increase in skin blood flow was observed in OB. Correlation analysis elucidated that the water content was strongly correlated with local skin indices, such as the ceramide composition, redness, blood flow, and TNFα in the stratum corneum, whereas roughness was correlated with the systemic indices, such as serum insulin, leptin, and IL-6. CONCLUSIONS: Characteristics of obesity-associated skin were (A) reduction of the barrier and moisturizing function accompanied by intercellular lipid imbalance, (B) increased redness accompanied by hemodynamic changes, and (C) surface roughness. It was suggested that each symptom is due to different causes in local and/or systemic physiological impairment related to the autonomic nerve-vascular system, inflammation and insulin resistance.

Biallelic Mutations in KDSR Disrupt Ceramide Synthesis and Result in a Spectrum of Keratinization Disorders Associated with Thrombocytopenia.

Mutations in ceramide biosynthesis pathways have been implicated in a few Mendelian disorders of keratinization, although ceramides are known to have key roles in several biological processes in skin and other tissues. Using whole-exome sequencing in four probands with undiagnosed skin hyperkeratosis/ichthyosis, we identified compound heterozygosity for mutations in KDSR, encoding an enzyme in the de novo synthesis pathway of ceramides. Two individuals had hyperkeratosis confined to palms, soles, and anogenital skin, whereas the other two had more severe, generalized harlequin ichthyosis-like skin. Thrombocytopenia was present in all patients. The mutations in KDSR were associated with reduced ceramide levels in skin and impaired platelet function. KDSR enzymatic activity was variably reduced in all patients, resulting in defective acylceramide synthesis. Mutations in KDSR have recently been reported in inherited recessive forms of progressive symmetric erythrokeratoderma, but our study shows that biallelic mutations in KDSR are implicated in an extended spectrum of disorders of keratinization in which thrombocytopenia is also part of the phenotype. Mutations in KDSR cause defective ceramide biosynthesis, underscoring the importance of ceramide and sphingosine synthesis pathways in skin and platelet biology.

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.