Disorganisation of basement membrane zone architecture impairs melanocyte residence in vitiligo.

The basement membrane zone is the interface between the epidermis and dermis, and it is disrupted in several skin conditions. Here, we report the results of a comprehensive investigation into the structural and molecular factors of the basement membrane zone in vitiligo, a dermatological disorder characterised by depigmented patches on the skin. Using electron microscopy and immunofluorescence staining, we confirmed abnormal basement membrane zone morphology and disrupted basement membrane zone architecture in human vitiliginous skin.

NKX2‑1 copy number alterations are associated with oncogenic, immunological and prognostic remodeling in non‑small cell lung cancer.

NK2 homeobox 1 (NKX2-1) copy number alterations (CNAs) are frequently observed in lung cancer. However, little is known about the complete landscape of focal alterations in NKX2-1 copy number (CN), their clinical significance and their therapeutic implications in non-small cell lung cancer (NSCLC). The correlations between NKX2-1 expression and EGFR driver mutations and programmed death ligand 1 (PD-L1) co-expression were studied using immunohistochemistry and PCR from the tumors of recruited Filipino patients (n=45).

The differential prognostic implications of PD-L1 expression in the outcomes of Filipinos with -mutant NSCLC treated with tyrosine kinase inhibitors.

Background: The tumor immune microenvironment influences tumor evolution in non-small cell lung cancer (NSCLC). Yet, the prognostic value of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor (EGFR)-mutant NSCLC remains controversial. Additionally, prognostic studies in Filipinos with EGFR-mutant NSCLC remain unexplored to this day.

Spin polarization gate device based on the chirality-induced spin selectivity and robust nonlocal spin polarization.

Nonlocal spin polarization phenomena are thoroughly investigated in the devices made of chiral metallic single crystals of CrNb3S6 and NbSi2 as well as of polycrystalline NbSi2. We demonstrate that simultaneous injection of charge currents in the opposite ends of the device with the nonlocal setup induces the switching behavior of spin polarization in a controllable manner. Such a nonlocal spin polarization appears regardless of the difference in the materials and device dimensions, implying that the current injection in the nonlocal configuration splits spin-dependent chemical potentials throughout the chiral crystal even though the current is injected into only a part of the crystal.

A Connecting Link between Hyaluronan Synthase 3-Mediated Hyaluronan Production and Epidermal Function.

Hyaluronan (HA), an essential component of the extracellular matrix of the skin, is synthesized by HA synthases (HAS1-3). To date, epidermal HA has been considered a major player in regulating cell proliferation and differentiation. However, a previous study reported that depletion of epidermal HA by hyaluronidase (St-HAase) has no influence on epidermal structure and function.

A Lower Irradiation Dose of 308 nm Monochromatic Excimer Light Might Be Sufficient for Vitiligo Treatment: A Novel Insight Gained from In Vitro and In Vivo Analyses.

A 308 nm monochromatic excimer light (MEL) is widely used to treat patients with vitiligo. However, dose optimization still needs to be clarified. This study aimed to obtain objective evidence regarding various doses of MEL irradiation, induced cell level changes in vitro, and skin level alterations in vivo.

Antiwrinkle efficacy of 1-ethyl-β-N-acetylglucosaminide, an inducer of epidermal hyaluronan production.

Background: Hyaluronan (HA) has a unique hydration capacity that contributes to firmness and bounciness of the skin. Epidermal HA declines with skin aging, which may lead to clinical signs of aging including skin wrinkles and loss of hydration and elasticity. Recently, we developed a new cosmetic agent 1-ethyl-β-N-acetylglucosaminide (β-NAG2), which enhances HA production in cultured human keratinocytes.

Assessment of the feasibility of frozen sections for the detection of spread through air spaces (STAS) in pulmonary adenocarcinoma.

Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection.

1-Ethyl-β-N-acetylglucosaminide increases hyaluronan production in human keratinocytes by being converted to N-acetylglucosamine via β-N-acetylglucosaminidase-dependent manner.

Regulation of hyaluronan (HA) is important for the maintenance of epidermal homeostasis. Here, we examined the mechanism by which 1-ethyl-β-N-acetylglucosaminide (β-NAG2), a newly developed N-acetylglucosamine (NAG) derivative, increases HA production in cultured human epidermal keratinocytes. When keratinocytes were treated with β-NAG2, mRNA expression of HA synthase 3, which is responsible for HA production in human keratinocytes, was not influenced, but the intracellular level of UDP-NAG, a substrate used for HA synthesis, was increased.

Accelerated human epidermal turnover driven by increased hyaluronan production.

Background: Hyaluronan (HA) is an essential component of extracellular matrix in the skin, but its functions in the epidermis remain elusive.

Objective: We examined the interaction of increased HA production mediated by 1-ethyl-β-N-acetylglucosaminide (β-NAG2), a newly developed highly selective inducer of HA production which is intracellularly converted to UDP-N-acetylglucosamine, a substrate of HA, with epidermal proliferation and differentiation.

Methods: The amount, molecular size and epidermal tissue distribution of HA and expression of CD44, a cell surface receptor for HA, were analyzed in β-NAG2-treated organ cultured human skin, reconstructed human skin equivalents or cultured human skin keratinocytes.

Accuracy and Reproducibility of Intraoperative Assessment on Tumor Spread Through Air Spaces in Stage 1 Lung Adenocarcinomas.

Introduction: Tumor spread through air spaces (STAS) is associated with worse prognosis in early-stage lung adenocarcinomas, particularly in sublobar resection. Intraoperative consultation for STAS has been advocated to guide surgical management. However, data on accuracy and reproducibility of intraoperative assessment of STAS remain limited.

Depth-resolved investigation of multiple optical properties and wrinkle morphology in eye-corner areas with multi-contrast Jones matrix optical coherence tomography.

Background: Multi-contrast Jones matrix optical coherence tomography (JM-OCT) can provide quantitative depth-resolved local optical properties by improving the measurement algorithm.

Materials And Methods: We examined the relationship between depth-resolved local optical properties of eye-corner skin measured by JM-OCT and corresponding wrinkle morphology of aged women (n = 21; age range, 71.7 ± 1.

HYBID (alias KIAA1199/CEMIP) and hyaluronan synthase coordinately regulate hyaluronan metabolism in histamine-stimulated skin fibroblasts.

The immune-regulatory compound histamine is involved in the metabolism of the essential skin component hyaluronan (HA). We previously reported that histamine up-regulates the expression of HYBID (hyaluronan-binding protein involved in hyaluronan depolymerization, also called CEMIP or KIAA1199), which plays a key role in HA degradation. However, no information is available about histamine's effects on HA synthase (HAS) expression, the molecular sizes of HA species produced, and histamine receptors and their signaling pathways in skin fibroblasts.

Inhibitory effects of Sanguisorba officinalis root extract on HYBID (KIAA1199)-mediated hyaluronan degradation and skin wrinkling.

Objectives: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation.

Inhibition of HYBID (KIAA1199)-mediated hyaluronan degradation and anti-wrinkle effect of Geranium thunbergii extract.

Background: Hyaluronan (HA) is an essential constituent of extracellular matrix in the skin. HA reduction in the dermis and overexpression of HYBID (KIAA1199), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling.

Aims: We aimed to obtain anti-wrinkle agent(s) by screening for inhibition of HYBID-mediated HA degradation.

Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women.

Background: Hyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women.

Methods: The skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID.

Reduction of hyaluronan and increased expression of HYBID (alias CEMIP and KIAA1199) correlate with clinical symptoms in photoaged skin.

Background: Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID (hyaluronan binding protein involved in hyaluronan depolymerization, alias CEMIP and KIAA1199) and the HA synthases HAS1 and HAS2. However, photoageing-dependent changes in HA and their molecular mechanisms, and the relationship between HA metabolism and clinical symptoms in photoaged skin remain elusive.

Objectives: We examined the amount, size and tissue distribution of HA and expression levels of HYBID, HAS1 and HAS2 in photoaged skin, and analysed their relationship with the degree of photoageing.

Lutein, a nonprovitamin A, activates the retinoic acid receptor to induce HAS3-dependent hyaluronan synthesis in keratinocytes.

Carotenoids have been reported to have potent antioxidant activities and to protect tissues and cells from certain diseases and environmental insults. The molecular mechanism of the action of provitamin A carotenoids such as β-carotene and β-cryptoxanthin is mediated in part by retinoic acid, an active form of provitamin A, but the molecular basis of the biological activities of non-provitamin A carotenoids such as lutein, zeaxanthin, and astaxanthin is not fully understood. In this study, we investigated to determine whether the actions of non-provitamin A carotenoids are mediated via retinoid signaling by monitoring retinoic acid receptor (RAR)-dependent hyaluronan production in cultured human keratinocytes.

KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization.

Hyaluronan (HA) has an extraordinarily high turnover in physiological tissues, and HA degradation is accelerated in inflammatory and neoplastic diseases. CD44 (a cell surface receptor) and two hyaluronidases (HYAL1 and HYAL2) are thought to be responsible for HA binding and degradation; however, the role of these molecules in HA catabolism remains controversial. Here we show that KIAA1199, a deafness gene of unknown function, plays a central role in HA binding and depolymerization that is independent of CD44 and HYAL enzymes.

Changes in epidermal hyaluronan metabolism following UVB irradiation.

Background: Hyaluronan (HA) plays a role in keratinocyte proliferation and differentiation, and have shown different biological activities depending on its molecular mass. While many studies have shown changes in the amount of HA after UVB irradiation, molecular mass change remains to be elucidated.

Objective: To investigate the change in the molecular mass of HA after UVB irradiation in mouse epidermis.

The presence of N(ε)-(Carboxymethyl) lysine in the human epidermis.

It is well known that advanced glycation end products (AGEs) are formed in long-lived dermal proteins such as collagen, and that their formation is related to skin aging. To examine the distribution of AGEs in skin tissue, we performed immunofluorescence studies on the human skin using an anti-AGEs antibody. Interestingly, AGEs signals were observed not only in the dermis but also in the epidermis.

Adiponectin resides in mouse skin and upregulates hyaluronan synthesis in dermal fibroblasts.

Adipose tissue is a hormonally active tissue that produces adipokines that influence the activity of other tissues. Adiponectin is an adipocyte-specific adipokine involved in systemic metabolism. We detected the expression of adiponectin receptors (AdipoR1 and AdipoR2) mRNA in cultured dermal fibroblasts.

Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb.

The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements.