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.

Impact of water exposure on skin barrier permeability and ultrastructure.

BACKGROUND: Skin occlusion caused by the use of diapers or sanitary napkins often results in irritant contact dermatitis. Furthermore, prolonged occlusion and exposure to body fluids are known to increase skin hydration and permeability, thus leading to irritant contact dermatitis. OBJECTIVE: To investigate the effects of water exposure on the skin and its barrier functions, in order to obtain more insights into the mechanisms of irritant contact dermatitis. METHODS: Water patches were applied to the volar forearm skin of 10 human subjects for 3 hours. Permeability of the stratum corneum (SC) was examined with methyl nicotinate (MN). Alterations in the hydration and ultrastructure of the SC were measured with Raman spectroscopy and multiphoton microscopy, respectively. RESULTS: Water profiles found with Raman spectroscopy showed notable increases in water content throughout the SC and skin surface. Multiphoton microscopy showed morphological changes in the intercellular space of the SC. Emerged pools seemed to contribute to increased MN absorption. CONCLUSION: Excessive skin hydration leading to changes in the SC ultrastructure might result in increased skin permeability to skin irritants and allergens.

Ethnic differences in stratum corneum functions between Chinese and Thai infants residing in Bangkok, Thailand.

BACKGROUND/OBJECTIVES: Ethnic and racial differences in infant skin have not been well characterized. The purpose of this study was to establish whether there are ethnic differences and similarities in the stratum corneum (SC) functions of Thai and Chinese infants. METHODS: Healthy infants 6 to 24 months of age (N = 60; 30 Thai, 30 Chinese) who resided in Bangkok, Thailand, were enrolled. Transepidermal water loss (TEWL) and SC hydration (capacitance) on the thigh, buttock, and upper arm were measured. Ceramide content was determined in the SC on the upper arm. RESULTS: SC hydration was not remarkably different between the two ethnicities at any site measured, but TEWL was significantly higher in Chinese infants than in Thai infants at all sites. Hydration of the SC was not significantly correlated with age in either ethnicity. TEWL had significant but weak correlations with age on the thigh and upper arm in Thai infants. Ceramide content was significantly higher in Chinese SC than in Thai SC. No relationship between ceramide content and TEWL or hydration was observed in either ethnicity. CONCLUSION: The significant differences in TEWL and ceramide contents between Chinese and Thai infant skin could prove useful in designing skin care and diapering products that are best suited for each ethnicity.

Properties of Skin in Chinese Infants: Developmental Changes in Ceramides and in Protein Secondary Structure of the Stratum Corneum.

The properties of infant skin regarding its structure and stratum corneum (SC) properties during development compared to adult skin have been reported only for a few races and body sites. The aim of this study was to understand the developmental changes of skin properties in Chinese infants, focusing on SC ceramides and protein secondary structure, which are important for skin barrier function. Three body sites with distinct characteristics (cheeks, inner upper arms, and buttocks) were assessed. Sixty pairs of Chinese infants and their mothers were measured for SC hydration, transepidermal water loss, ceramide levels, sebum with an ester bond, and protein secondary structure of superficial SC. Skin hydration decreased with age at all body sites. TEWL was similar between the 2-12- and 13-24-month-old groups but was higher than the adult group at the buttocks and inner upper arms and was equal to the adult group at the cheeks. These differences coincided with differences in protein secondary structure. Ceramide and sebum levels were lower in the infant groups. We conclude that both the SC functions and the components of infant skin are still developing and are not fully adapted as in adult skin at each body site examined.

Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): a highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

Dipeptidyl peptidase IV (DPP-4) inhibition is suitable mechanism for once daily oral dosing regimen because of its low risk of hypoglycemia. We explored linked bicyclic heteroarylpiperazines substituted at the γ-position of the proline structure in the course of the investigation of l-prolylthiazolidines. The efforts led to the discovery of a highly potent, selective, long-lasting and orally active DPP-4 inhibitor, 3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine (8 g), which has a unique structure characterized by five consecutive rings. An X-ray co-crystal structure of 8 g in DPP-4 demonstrated that the key interaction between the phenyl ring on the pyrazole and the S(2) extensive subsite of DPP-4 not only boosted potency, but also increased selectivity. Compound 8 g, at 0.03 mg/kg or higher doses, significantly inhibited the increase of plasma glucose levels after an oral glucose load in Zucker fatty rats. Compound 8 g (teneligliptin) has been approved for the treatment of type 2 diabetes in Japan.