Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.

• Klíčová slova
• BRD4, gallic acid, hyperproliferation, inflammation, keratinocytes, psoriasis,
• MeSH
• apoptóza * účinky léků   MeSH
• buněčné linie keratinocytů HaCaT MeSH
• buněčné linie MeSH
• dospělí MeSH
• interleukin-17 metabolismus   MeSH
• jaderné proteiny metabolismus   genetika   MeSH
• keratinocyty * účinky léků   metabolismus   MeSH
• kyselina gallová * farmakologie   MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• pohyb buněk * účinky léků   MeSH
• proliferace buněk * účinky léků   MeSH
• proteiny buněčného cyklu * metabolismus   genetika   MeSH
• proteiny obsahující bromodoménu MeSH
• psoriáza * metabolismus   patologie   farmakoterapie   MeSH
• regulace genové exprese účinky léků   MeSH
• transkripční faktory * metabolismus   MeSH
• zánět * patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BRD4 protein, human MeSH Prohlížeč
• interleukin-17 MeSH
• jaderné proteiny MeSH
• kyselina gallová * MeSH
• mikro RNA MeSH
• proteiny buněčného cyklu * MeSH
• proteiny obsahující bromodoménu MeSH
• transkripční faktory * MeSH

BACKGROUND: Psoriasis is a pathological condition characterized by immune system dysfunction and inflammation. Patients with psoriasis are more likely to develop a wide range of disorders associated with inflammation. Serum levels of various substances and their combinations have been associated with the presence of the disease (psoriasis) and have shown the potential to reflect its activity. The aim of the present study is to contribute to the elucidation of pathophysiological links between psoriasis, its pro-inflammatory comorbidity metabolic syndrome (MetS), and the expression of clusterin and elafin, which are reflected in the pathophysiological "portfolio" of both diseases. MATERIAL AND METHODS: Clinical examinations (PASI score), ELISA (clusterin, elafin), and biochemical analyses (parameters of MetS) were performed. RESULTS: We found that patients with psoriasis were more often afflicted by MetS, compared to the healthy controls. Clusterin and elafin levels were higher in the patients than in the controls but did not correlate to the severity of psoriasis. CONCLUSION: Our data suggest that patients with psoriasis are more susceptible to developing other systemic inflammatory diseases, such as MetS. The levels of clusterin and elafin, which are tightly linked to inflammation, were significantly increased in the patients, compared to the controls, but the presence of MetS in patients did not further increase these levels.

• Klíčová slova
• clusterin, elafin, metabolic syndrome, psoriasis,
• MeSH
• dospělí MeSH
• elafin genetika   MeSH
• index tělesné hmotnosti MeSH
• klusterin genetika   MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom komplikace   genetika   metabolismus   patologie   MeSH
• psoriáza komplikace   genetika   metabolismus   patologie   MeSH
• regulace genové exprese genetika   MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• zánět genetika   metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CLU protein, human MeSH Prohlížeč
• elafin MeSH
• klusterin MeSH
• PI3 protein, human MeSH Prohlížeč

Gentiana lutea is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that Gentiana lutea extract (GE) also modulates the lipid metabolism of human keratinocytes in vitro and in vivo. In the present study, we investigated the role of GE on ceramide synthesis in human primary keratinocytes (HPKs) and psoriasis-like keratinocytes. We could demonstrate that GE increased the concentrations of glucosylceramides and the ceramide AS/AdS subclass without affecting the overall ceramide content in HPKs. The expression of ceramide synthase 3 (CERS3) and elongases (ELOVL1 and 4) was reduced in psoriasis lesions compared to healthy skin. Psoriasis-like HPKs, generated by stimulating HPKs with cytokines that are involved in the pathogenesis of psoriasis (IL-17, TNF-α, IL-22 and IFN-γ) showed increased levels of IL-6, IL-8 and increased expression of DEFB4A, as well as decreased expression of ELOVL4. The treatment with GE partly rescued the reduced expression of ELOVL4 in psoriasis-like HPKs and augmented CERS3 expression. This study has shown that GE modulates ceramide synthesis in keratinocytes. Therefore, GE might be a novel topical treatment for skin diseases with an altered lipid composition such as psoriasis.

• Klíčová slova
• CerS, ELOVL, Gentiana lutea, ceramides, skin,
• MeSH
• ceramidy metabolismus   MeSH
• elongasy mastných kyselin genetika   metabolismus   MeSH
• Gentiana chemie   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• oční proteiny genetika   metabolismus   MeSH
• primární buněčná kultura MeSH
• psoriáza genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• sfingosin-N-acyltransferasa genetika   metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ceramidy MeSH
• CERS3 protein, human MeSH Prohlížeč
• elongasy mastných kyselin MeSH
• ELOVL1 protein, human MeSH Prohlížeč
• ELOVL4 protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• oční proteiny MeSH
• rostlinné extrakty MeSH
• sfingosin-N-acyltransferasa MeSH

In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play mutual roles interrelated with metabolic syndrome (MetS). This study aims to map the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage to nucleic acids (DNA/RNA damage; 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), and the parameters of MetS (waist circumference, fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, diastolic and systolic blood pressure) in a group of 37 patients with psoriasis (62% of MetS) and in 43 healthy controls (42% of MetS). Levels of CRP, DNA/RNA damage, fasting glucose, and triglycerides were significantly elevated in patients. MetS in conjunction with psoriasis was associated with high levels of CRP, significantly higher than in control subjects without MetS. Patients with MetS exhibited further DNA/RNA damage, which was significantly higher in comparison with the control group. Our study supports the independent role of psoriasis and MetS in the increase of CRP and DNA/RNA damage. The psoriasis contributes to an increase in the levels of both effects more significantly than MetS. The psoriasis also diminished the relationship between CRP and oxidative damage to nucleic acids existent in controls.

• Klíčová slova
• inflammation, metabolic syndrome, oxidative stress, psoriasis,
• MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom komplikace   MeSH
• oxidační stres * MeSH
• poškození DNA * MeSH
• psoriáza etiologie   metabolismus   patofyziologie   MeSH
• zánět komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Psoriasis is an inflammatory skin disease that affects 2-5% of the worldwide population. It is a chronic immune-mediated hyperproliferative inflammatory skin disease of unknown etiology, characterized by the appearance of sore patches of thick, red skin with silvery scales.

• MeSH
• fibroblasty účinky léků   metabolismus   MeSH
• kůže cytologie   patologie   MeSH
• lidé MeSH
• oleje rostlin chemie   farmakologie   MeSH
• oxidace-redukce účinky léků   MeSH
• psoriáza metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• oleje rostlin MeSH

Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.

• MeSH
• 2',5'-oligoadenylátsynthetasa genetika   metabolismus   MeSH
• CpG ostrůvky * MeSH
• epigeneze genetická * MeSH
• lidé MeSH
• metylace DNA MeSH
• nádory hlavy a krku genetika   metabolismus   patologie   MeSH
• nádory jazyka genetika   metabolismus   patologie   MeSH
• promotorové oblasti (genetika) MeSH
• psoriáza genetika   metabolismus   patologie   MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom genetika   metabolismus   patologie   MeSH
• studie případů a kontrol MeSH
• tonzilární nádory genetika   metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2',5'-oligoadenylátsynthetasa MeSH
• OAS2 protein, human MeSH Prohlížeč

BACKGROUND: Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). OBJECTIVE: To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). METHODS: The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. RESULTS: Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). CONCLUSION: Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.

• Klíčová slova
• 25-Hydroxy vitamin D, Chromosomal aberration, Oxidative stress, Polycyclic aromatic hydrocarbons, UV radiation,
• MeSH
• aplikace kožní MeSH
• biologické markery krev   moč   MeSH
• časové faktory MeSH
• celotělové ozáření MeSH
• chronická nemoc MeSH
• dehet uhelný aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• keratolytika aplikace a dávkování   škodlivé účinky   MeSH
• kombinovaná terapie MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• oxidační stres účinky léků   účinky záření   MeSH
• polycyklické aromatické uhlovodíky aplikace a dávkování   škodlivé účinky   MeSH
• poškození DNA MeSH
• psoriáza diagnóza   metabolismus   terapie   MeSH
• pyreny moč   MeSH
• senioři MeSH
• stabilita RNA účinky léků   účinky záření   MeSH
• stárnutí kůže účinky léků   účinky záření   MeSH
• terapie ultrafialovými paprsky škodlivé účinky   metody   MeSH
• vitamin D analogy a deriváty   krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-hydroxypyrene MeSH Prohlížeč
• 25-hydroxyvitamin D MeSH Prohlížeč
• biologické markery MeSH
• dehet uhelný MeSH
• keratolytika MeSH
• polycyklické aromatické uhlovodíky MeSH
• pyreny MeSH
• vitamin D MeSH

The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).

• MeSH
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid analýza   chemie   MeSH
• adukty DNA analýza   chemie   MeSH
• benzopyren chemie   toxicita   MeSH
• chromozomální aberace * MeSH
• dehet uhelný farmakologie   terapeutické užití   MeSH
• dítě MeSH
• DNA chemie   MeSH
• keratolytika farmakologie   terapeutické užití   MeSH
• kohortové studie MeSH
• lidé MeSH
• lymfocyty cytologie   metabolismus   MeSH
• masti farmakologie   terapeutické užití   MeSH
• mladiství MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• psoriáza farmakoterapie   metabolismus   patologie   MeSH
• ultrafialové záření * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid MeSH
• adukty DNA MeSH
• benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA MeSH Prohlížeč
• benzopyren MeSH
• dehet uhelný MeSH
• DNA MeSH
• keratolytika MeSH
• masti MeSH

Topical skin lipid supplementation may provide opportunities for controlling ceramide (Cer) deficiency in skin diseases such as atopic dermatitis or psoriasis. Here we describe the synthesis of a long-chain 7-nitrobenzo[c][1,2,5]oxadiazol-4-yl (NBD)-labeled Cer and its different penetration through human skin compared to widely used short-chain fluorescent Cer tools.

• MeSH
• 4-chlor-7-nitrobenzofurazan chemická syntéza   metabolismus   MeSH
• atopická dermatitida metabolismus   MeSH
• bisbenzimidazol metabolismus   MeSH
• ceramidy chemická syntéza   metabolismus   MeSH
• fluorescence MeSH
• fluorescenční barviva chemická syntéza   metabolismus   MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• permeabilita MeSH
• psoriáza metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-chlor-7-nitrobenzofurazan MeSH
• bisbenzimidazol MeSH
• ceramidy MeSH
• fluorescenční barviva MeSH

Psoriasis is considered an auto-immune disease with consequential keratinocyte hyperproliferation resulting in specific architecture of psoriatic skin. This process is associated with phenotypical keratinocyte changes including an altered carbohydrate expression pattern studied by labelled plant lectins. Expression of endogenous lectins and their reactive glycoligands are differentiation-dependent in squamous epithelia including epidermis. However, no data are available on psoriatic skin, although this disease represents an important medical problem. We investigated the expression of galectin-1, -3, -7 and the presence of their glycoligands in the psoriatic skin and compared the results with the normal skin samples. The results were correlated to expression patterns of cytokeratin 10 and cytokeratin peptide 37 as markers of keratinocyte differentiation as well as to the expression of proliferation marker Ki67. Contrary to normal epidermis, the psoriatic epithelium expressed no galectin-3 and no glycoligands for galectin-1. Strong expression of galectin-3/galectin-3-reactive glycoligands in capillaries of psoriatic dermis represents one of the most important findings demonstrating the activation of endothelium in the course of the disease. The keratin expression pattern was not affected in psoriatic skin compared with normal epidermis. In conclusion, the altered galectin expression and binding pattern in psoriatic skin indicates the modified process of keratinocyte maturation in hyperactivated psoriatic epithelium. The enhanced expression of galectin-3/galectin-3-reactive glycoligands in dermal capillaries of psoriatic skin can be important for rearrangement of the capillary network and migration of inflammatory cells to psoriatic skin.

• MeSH
• biologické markery MeSH
• buněčná diferenciace MeSH
• fenotyp MeSH
• fluorescenční protilátková technika nepřímá MeSH
• galektin 1 metabolismus   MeSH
• galektin 3 metabolismus   MeSH
• galektiny metabolismus   MeSH
• keratinocyty metabolismus   patologie   MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• psoriáza metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• galektin 1 MeSH
• galektin 3 MeSH
• galektiny MeSH
• LGALS1 protein, human MeSH Prohlížeč
• LGALS7 protein, human MeSH Prohlížeč