• MeSH
• acyltransferasy MeSH
• arachidonát-12-lipoxygenasa genetika   MeSH
• epidermis * MeSH
• fosfolipasy MeSH
• kůže MeSH
• lamelární ichtyóza * MeSH
• lipidy MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8+ T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF.

• Publikační typ
• časopisecké články MeSH

The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC through the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32-37 °C but not at room temperature was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids (required for lipid barrier assembly) to rigid and tightly packed lipids in the mature SC (necessary for the water and permeability barriers).

• MeSH
• epidermis * MeSH
• lidé MeSH
• lipidy MeSH
• nízká teplota * MeSH
• savci MeSH
• teplota MeSH
• voda MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• epidermis * MeSH
• kůže * MeSH
• lidé MeSH
• lipidy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Nardin et al's (2021) study on melanoma reports anti-TERT CD4 T helper type (Th) 1 responses in more than half of patients. Besides indicating a trend for improved survival, increased anti-TERT CD4 Th1 responses predicted better outcomes for patients treated with immune checkpoint inhibitors. Thus, harnessing systemic anti-TERT CD4 Th1 responses together with tumor-specific elevation of telomerase can potentially open new avenues for biomarkers and treatment in melanoma.

• MeSH
• imunita MeSH
• imunoterapie MeSH
• lidé MeSH
• melanom * farmakoterapie   MeSH
• telomerasa * MeSH
• Th1 buňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH

Although lipids are crucial molecules for cell structure, metabolism, and signaling in most organs, they have additional specific functions in the skin. Lipids are required for the maintenance and regulation of the epidermal barrier, physical properties of the skin, and defense against microbes. Analysis of the lipidome-the totality of lipids-is of similar complexity to those of proteomics or other omics, with lipid structures ranging from simple, linear, to highly complex structures. In addition, the ordering and chemical modifications of lipids have consequences on their biological function, especially in the skin. Recent advances in analytic capability (usually with mass spectrometry), bioinformatic processing, and integration with other dermatological big data have allowed researchers to increasingly understand the roles of specific lipid species in skin biology. In this paper, we review the techniques used to analyze skin lipidomics and epilipidomics.

• MeSH
• big data MeSH
• biomedicínský výzkum MeSH
• epigeneze genetická MeSH
• hmotnostní spektrometrie MeSH
• kůže metabolismus   patologie   MeSH
• lidé MeSH
• lipidomika metody   MeSH
• metabolismus lipidů MeSH
• výpočetní biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Lipid membrane remodeling belongs to the most fundamental processes in the body. The skin barrier lipids, which are ceramide dominant and highly rigid, must attain an unusual multilamellar nanostructure with long periodicity to restrict water loss and prevent the entry of potentially harmful environmental factors. Our data suggest that the skin acid mantle, apart from regulating enzyme activities and keeping away pathogens, may also be a prerequisite for the multilamellar assembly of the skin barrier lipids. Atomic force microscopy on monolayers composed of synthetic or human stratum corneum lipids showed multilayer formation (approximately 10-nm step height) in an acidic but not in a neutral environment. X-ray diffraction, Fourier transform infrared spectroscopy, and permeability studies showed markedly altered lipid nanostructure and increased water loss at neutral pH compared with that at acidic pH. These findings are consistent with the data on the altered organization of skin lipids and increased transepidermal water loss under conditions such as inadequate skin acidification, for example, in neonates, the elderly, and patients with atopic dermatitis.

• MeSH
• atopická dermatitida patologie   MeSH
• ceramidy chemie   metabolismus   MeSH
• cholesterol chemie   metabolismus   MeSH
• difrakce rentgenového záření MeSH
• epidermis chemie   metabolismus   patologie   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny mastné neesterifikované chemie   metabolismus   MeSH
• lidé MeSH
• mastné kyseliny MeSH
• mikroskopie atomárních sil MeSH
• novorozenec MeSH
• permeabilita MeSH
• perspiratio insensibilis * MeSH
• senioři MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mastocytosis is a rare neoplasm characterized by the expansion and accumulation of mast cells in various organ systems. Systemic mastocytosis (SM) may or may not present with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, data on 1,510 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1,195 of 1,510 patients (79.1%). Of these, 286 had cutaneous mastocytosis, and 721 had SM with skin involvement. Adult patients with skin involvement who did not have a bone marrow examination (n = 188) were defined as having mastocytosis in the skin. In 315 patients, SM without skin involvement was found. The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years, no patient with cutaneous mastocytosis had died, but 2.6% of the patients with mastocytosis in the skin, 5.7% of the patients with SM with skin involvement, and 28.95% of the patients with SM without skin involvement had died. Overall survival was longer in patients with skin involvement (cutaneous mastocytosis and/or mastocytosis in the skin and/or SM with skin involvement) than in patients with SM without skin involvement (P < 0.0001). These data argue for a thorough examination of both the skin and bone marrow in adult patients with mastocytosis.

• MeSH
• analýza přežití MeSH
• biopsie MeSH
• časové faktory MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• kostní dřeň patologie   MeSH
• kožní mastocytóza diagnóza   epidemiologie   patologie   MeSH
• kůže patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastocyty patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• prognóza MeSH
• registrace statistika a číselné údaje   MeSH
• senioři MeSH
• systémová mastocytóza diagnóza   mortalita   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

Gene editing with zinc finger nucleases, transcription activator-like effector nucleases, clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated proteins system, or meganucleases can, in principle, mediate any genome modification. Recent studies have shown that COL7A1 mutations in cells of patients with recessive dystrophic epidermolysis bullosa can be corrected by homology-directed DNA repair.

• MeSH
• epidermolysis bullosa dystrophica genetika   MeSH
• kolagen typ VII genetika   MeSH
• lidé MeSH
• oprava DNA * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH

House dust mites (HDMs) belong to the most potent indoor allergen sources worldwide and are associated with allergic manifestations in the respiratory tract and the skin. Here we studied the importance of the high-molecular-weight group 11 allergen from Dermatophagoides pteronyssinus (Der p 11) in HDM allergy. Sequence analysis showed that Der p 11 has high homology to paramyosins from mites, ticks, and other invertebrates. A synthetic gene coding for Der p 11 was expressed in Escherichia coli and rDer p 11 purified to homogeneity as folded, alpha-helical protein as determined by circular dichroism spectroscopy. Using antibodies raised against rDer p 11 and immunogold electron microscopy, the allergen was localized in the muscle beneath the skin of mite bodies but not in feces. IgE reactivity of rDer p 11 was tested with sera from HDM-allergic patients from Europe and Africa in radioallergosorbent test-based dot-blot assays. Interestingly, we found that Der p 11 is a major allergen for patients suffering from atopic dermatitis (AD), whereas it is only a minor allergen for patients suffering from respiratory forms of HDM allergy. Thus, rDer p 11 might be a useful serological marker allergen for the identification of a subgroup of HDM-allergic patients suffering from HDM-associated AD.

• MeSH
• antigeny roztočů domácího prachu chemie   genetika   imunologie   MeSH
• atopická dermatitida epidemiologie   imunologie   MeSH
• biologické markery MeSH
• cirkulární dichroismus MeSH
• Dermatophagoides pteronyssinus genetika   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• imunoglobulin E krev   imunologie   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• molekulární sekvence - údaje MeSH
• proteiny členovců MeSH
• protilátky krev   imunologie   MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• séroepidemiologické studie MeSH
• tropomyosin chemie   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH