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PubMed Journal Database | The Journal of investigative dermatology RSS

19:16 EDT 20th March 2019 | BioPortfolio

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Showing PubMed Articles 1–25 of 519 from The Journal of investigative dermatology

Amphiregulin from basophils amplifies basophil-mediated chronic skin inflammation.

Chronic UVA1 irradiation of human dermal fibroblasts: persistence of DNA damage and validation of a cell-cultured based model of photoaging.

Peptidylarginine Deiminase Inhibitor Cl-amidine Attenuates Cornification and Interferes with the Regulation of Autophagy in Reconstructed Human Epidermis.

Deimination, a post-translational modification catalyzed by a family of enzymes called peptidylarginine deiminases (PADs), is the conversion of arginine into citrulline residues in a protein. Deimination has been associated with numerous physiological and pathological processes. Our aim was to study its implication in the homeostasis of human epidermis, where three PADs are expressed, namely PAD1, 2 and 3. Three-dimensional reconstructed human epidermis (RHEs) were treated for two days with increased concen...

Racial/Ethnic Variation in Use of Ambulatory and Emergency Care for Atopic Dermatitis Among U.S. Children.

Previous studies indicate racial/ethnic differences in healthcare utilization for pediatric atopic dermatitis (AD) but do not account for disease severity impact. We sought to examine the relationship between race/ethnicity and healthcare utilization, both overall and by specific visit type, while accounting for AD control. A longitudinal cohort study of children with AD in the U.S. was performed to evaluate the association between race/ethnicity and healthcare utilization for AD. AD control and healthcare ...

HLA-C*01:02 and HLA-A*02:07 Confer Risk Specific for Psoriatic Patients in southern China.

Bone morphogenetic protein-6 inhibits fibrogenesis in scleroderma offering new treatment options of fibrotic skin disease.

Bone morphogenetic protein-6 (BMP6) is known to be crucial for regulating embryonic skin development. This study assessed the role of BMP6 in dermal fibrosis. We detected that BMP6 is significantly increased in skin-derived fibroblasts of patients with localized scleroderma. Moreover, it was shown that BMP6 significantly impacts proliferation, migration, cytoskeletal organization, and collagen expression as well as activity of the major pro-fibrogenic transcription factor AP-1 in dermal fibroblasts. The imp...

Loss of epidermal hypoxia-inducible factor-1α blocks UVB-induced tumorigenesis by affecting DNA repair capacity and oxidative stress.

Hypoxia-inducible factor-1α (HIF-1α) is constitutively expressed in mouse and human epidermis. It plays a crucial role in skin physiology including the response of keratinocytes to ultraviolet (UV) radiation. However, little information is available about its role in photocarcinogenesis. Using a multistage model of UVB radiation-induced skin cancer, we show that the knockout of Hif-1α in the epidermis prevents tumorigenesis, but at the same time triggers the formation of hyperkeratotic plaques. Our resul...

Cis-khellactone inhibited the proinflammatory macrophages via promoting autophagy to ameliorate imiquimod-induced psoriasis.

Psoriasis is a chronic inflammatory skin disease with unresolved pathogenesis. Studies on the pathogenesis of psoriasis have been extensively carried out, but treatments are still not satisfactory. In this study, we found improvement after treatment with cis-khellactone, a small molecular natural product, in imiquimod (IMQ)-challenged C57BL/6 mice. Cis-khellactone clearly reduced the level of cytokines in psoriatic skin, including IL-23, TNF-α, IL-1β and IL-6, while limiting inhibition of IL-17A, which is...

Keratinocyte integrin α3β1 promotes secretion of IL-1α to effect paracrine regulation of fibroblast gene expression and differentiation.

Following cutaneous injury, keratinocytes secrete paracrine factors that regulate wound cell functions; dysregulation of this signaling can lead to wound pathologies. Previously, we established that keratinocyte integrin α3β1 promotes wound angiogenesis through paracrine stimulation of endothelial cells. We hypothesize here that α3β1-dependent paracrine signaling from keratinocytes regulates the differentiation state of myofibroblasts. We report that epidermal α3 knockout mice exhibit more wound myofib...

Imaging mass spectrometry-based lipidomic approach to classification of architectural features in nevi.

Immunogenicity of Guselkumab Is Not Clinically Relevant in Patients with Moderate-to-Severe Plaque Psoriasis.

In pivotal Phase-3 studies (VOYAGE-1, VOYAGE-2), patients (N=1,829) with moderate-to-severe plaque psoriasis were randomized to subcutaneous guselkumab 100mg (Weeks0, 4, then every-8-weeks), placebo with guselkumab crossover at Week16, or adalimumab with guselkumab crossover at Week28 or Week52. The design of VOYAGE-2 incorporated a randomized withdrawal and retreatment period for patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) score at Week28. To assess guselkumab i...

Regulatory B1a cells suppress melanoma tumor immunity via IL-10 production and inhibiting Th1 cytokine production in tumor-infiltrating CD8 T cells.

In tumor immunity, the participation of IL-10-producing regulatory B cells (Bregs), which play an important role in suppressing immune responses, is unclear. In this study, we demonstrated an increase in B16F10 melanoma growth and a decrease in the proportion of IFN-γ- and TNF-α-secreting tumor-infiltrating CD8 T cells in B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice in which Bregs were expanded. The number of tumor-infiltrating Bregs significantly increased in B cell-specific PTEN-...

Efficient gene reframing therapy for recessive dystrophic epidermolysis bullosa using CRISPR/Cas9.

The CRISPR/Cas9 system induces site-specific double-strand breaks (DSBs), which stimulate cellular DNA repair through either the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. The NHEJ pathway, which is activated more frequently than HR, is prone to introducing small insertions and/or deletions at the DSB site, leading to changes in the reading frame. We hypothesized that the NHEJ pathway is applicable to genetic diseases caused by a frameshift mutation through restoration of t...

Effective Tyrosinase Inhibition by Thiamidol Results in Significant Improvement of Mild to Moderate Melasma.

Melasma is a pigmentary disorder characterized by hyperpigmented patchy skin in sun-exposed areas, especially the face. Treatment of melasma can be challenging since long-term therapy is required, reoccurrence is common and existing therapies are insufficient and unsatisfactory. To investigate new treatment options, we performed an exploratory double-blinded, randomized split-face study to assess the efficacy of the tyrosinase inhibitor Thiamidol compared to hydroquinone in women with mild to moderate melas...

Expression level of prostaglandin D2 receptor 2 regulates hair regression.

A double-blind randomized trial demonstrates the role of zonal priming & direct topical application of epigallocatechin-3-gallate in modulation of cutaneous scarring in human skin.

Epigallocatechin-3-gallate (EGCG), a polyphenol, influences cutaneous wound healing due to its anti-angiogenic, anti-inflammatory and anti-oxidant properties. We previously demonstrated the role of EGCG in scarring in ex vivo human scar models. Here, we evaluate direct application of topical EGCG compared with zonal-priming, a unique concept in immediate treatment of zone-of-injury at the time of wounding prior to scar formation.

Human keratinocytes use sphingosine 1-phosphate and its receptors to communicate S. aureus invasion and activate host defense.

Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator generated when a cell membrane or its components are damaged by various factors. S1P regulates diverse cell activities via S1P receptors (S1PRs). Keratinocytes express S1PR1-5. Though it is known that S1PRs control keratinocyte differentiation, apoptosis, and wound healing, S1PR functions in keratinocyte infections have not been fully elucidated. We propose that the S1P-S1PR axis in keratinocytes works as a biosensor for bacterial invasion. Indeed,...

Dynamic evolution of clonal composition and neoantigen landscape in recurrent metastatic melanoma with a rare combination of driver mutations.

In melanoma, initiating oncogenic mutations in BRAF or NRAS are detected in premalignant lesions that accumulate additional mutations and genomic instability as the tumour evolves to the metastatic state. Here we investigate evolution of clonal composition and neoantigen landscape in an atypical melanoma displaying recurrent cutaneous lesions over a 6-year period without development of extra-cutaneous metastases. Whole exome sequencing of 4 cutaneous lesions taken over the 6-year period identified a collect...

Nicotinamide Metabolism Modulates the Proliferation / Differentiation Balance and Senescence of Human Primary Keratinocytes.

Nicotinamide (NAM) is the main precursor of NAD, a co-enzyme essential for DNA repair, glycolysis and oxidative phosphorylation (OXPHOS). NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3D organotypic skin models, we show that NAM inhibits differentiation of the upper epidermal layers and maintains proliferation in the basal layer. In 2D culture, NAM reduces the expression of early and late epidermal differentiation markers and increases the proliferativ...

Hyperglycemia is associated with psoriatic inflammation in both humans and mice.

Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself correlates with hyperglycemia in humans and mice. In patients, severity of psoriasis was correlated with high blood glucose levels and treatment of psoriasis by phototherapy improved insulin secretion. I...

Molecular genomic profiling of melanocytic nevi.

The benign melanocytic nevus is the commonest tumor in humans and rarely transforms into cutaneous melanoma. Elucidation of the nevus genome is required to better understand the molecular steps of progression to melanoma. We performed whole genome sequencing on a series of 14 benign melanocytic nevi, consisting of both congenital and acquired types. All nevi had driver mutations in the MAPK signalling pathway, either BRAF V600E or NRAS Q61R/L. No additional definite driver mutations were identified. Somatic...

SOX2 epidermal overexpression promotes cutaneous wound healing via activation of EGFR/MEK/ERK signaling mediated by EGFR ligands.

Oral mucosa contains a unique transcriptional network that primes oral wounds for rapid resolution in humans. Our previous work identified genes that were consistently upregulated in the oral mucosa and demonstrated that induction of one of the identified genes, transcription factor SOX2, promoted cutaneous wound healing in mice. In this study, we investigated the molecular and cellular mechanisms by which SOX2 accelerates wound healing in skin. RNA-seq analysis showed that SOX2 induced a proliferative and ...

Differential hairless mouse strain-specific susceptibility to skin cancer and sunburn.

The NLRP1 inflammasome pathway is silenced in cutaneous squamous cell carcinoma.

The inflammasome protein NLRP1 is an important innate immune sensor in human keratinocytes and mediates, together with the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, the activation and secretion of the pro-inflammatory cytokines IL-1β and IL-18. These cytokines and inflammasomes can have in part opposing roles during tumorigenesis in mice. In contrast, ASC expression is impaired in different types of cancer in humans. In this study, we analyzed inflammaso...

Zinc-alpha-2 glycoprotein regulates the skin barrier and immunity in atopic dermatitis.

Adipokines modulate immune responses and lipid metabolism in allergic disease; however, little is known about its role in the skin barrier and atopic dermatitis (AD). We identified zinc-alpha-2 glycoprotein (ZAG), an adipokine that regulates lipid mobilization, as a biomarker for AD. ZAG levels were consistently decreased in sera, T cells, and skin in human AD patients compared with healthy controls. ZAG was primarily detected in the stratum corneum along with filaggrin (FLG) and loricrin (LOR). Knockdown o...


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