- MeSH
- epidermis * účinky záření metabolismus MeSH
- kalpain * metabolismus antagonisté a inhibitory MeSH
- keratinocyty účinky záření metabolismus MeSH
- lidé MeSH
- škára účinky záření patologie metabolismus cytologie MeSH
- ultrafialové záření * škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- dopisy MeSH
The negative impact of cigarette smoking on the skin includes accelerated aging, pigmentation disorders, and impaired wound healing, but its effect on the skin barrier is not completely understood. Here, we studied the changes in selected epidermal proteins and lipids between smokers (45-66 years, smoking > 10 years, > 10 cigarettes per day) and non-smokers. Volar forearm epidermal and stratum corneum samples, obtained by suction blister and tape stripping, respectively, showed increased thickness in smokers. In the epidermis of smokers, we observed a significant upregulation of filaggrin, loricrin, and a trend of increased involucrin but no differences were found in the case of transglutaminase 1 and kallikrein-related peptidase 7, on the gene and protein levels. No significant changes were observed in the major skin barrier lipids, except for increased cholesterol sulfate in smokers. Liquid chromatography coupled with mass spectrometry revealed shorter acyl chains in ceramides, and an increased proportion of sphingosine and 6-hydroxysphingosine ceramides (with C4 trans-double bond) over dihydrosphingosine and phytosphingosine ceramides in smokers, suggesting altered desaturase 1 activity. Smokers had more ordered lipid chains found by infrared spectroscopy. In conclusion, cigarette smoking perturbs the homeostasis of the barrier proteins and lipids even at a site not directly exposed to smoke.
INTRODUCTION: Constantly increasing air pollution (AP) poses a concern affecting not only our health but also our skin. A typical manifestation of the skin damage induced by AP is its premature aging, irritation, skin barrier impairment, pigmentation disorders, and development or exacerbation of various skin diseases. For these reasons, it is crucial to protect the skin from the negative effects of AP. In this study, we evaluated the ability of some compounds commonly used in dermatological or cosmetic preparations with various biological activities to reduce AP-induced skin damage. METHODS: We established a new experimental model using porcine skin explants exposed to cigarette smoke (CS) in which we determined the level of reactive oxygen species (ROS) in the stratum corneum, skin barrier lipids peroxidation, and gene expression of the pro-inflammatory cytokine interleukin 6 in the epidermis. Then, we tested several polysaccharides and their derivatives such as sodium hyaluronate (SH) of different molecular weight (MW, 1.6 MDa, 300 kDa, 15 kDa, 5 kDa), yeast glucomannan, schizophyllan, and carboxymethyl β-glucan, then vitamin C derivative sodium ascorbyl phosphate, niacinamide, and D-panthenol for their ability to prevent CS-induced skin damage. For the evaluation and comparison of their mechanism of action, film-forming effect was determined by TEWL and gloss measurements and the antioxidant properties were assessed by DPPH assay. RESULTS: In the skin samples exposed to CS, we observed significant negative changes such as the presence of large amount of ROS in the stratum corneum, high level of skin barrier lipids peroxidation and upregulated IL6 gene expression. Pretreatment of the skin samples with all the tested substances significantly prevented CS-induced skin damage. The most effective were high MW SH probably due to its best film-forming effect and sodium ascorbyl phosphate with the best antioxidant properties. CONCLUSION: AP leads to a significant skin damage which can be effectively prevented using some conventional cosmetic and dermatological ingredients with various mechanisms of action.
BACKGROUND: The human skin is greatly affected by external factors such as UV radiation (UVR), ambient temperature (T), and air humidity. These factors oscillate during the year giving rise to the seasonal variations in the skin properties. The aim of this study was to evaluate the effect of seasons, environmental T, relative and absolute humidity on the skin parameters of Caucasian women, perform a literature review and discuss the possible factors lying behind the found changes. MATERIALS AND METHODS: We measured stratum corneum (SC) hydration, transepidermal water loss (TEWL), sebum level, erythema index, and elasticity parameters R2 and R7 on the forehead and the cheek of Caucasian women from the Czech Republic throughout the year. We also performed a non-systematic literature review focused on the seasonal variations in these skin parameters. RESULTS: We confirmed a well-documented low SC hydration and sebum production in winter. In spring, we found the lowest TEWL (on the forehead) and the highest SC hydration but also the highest erythema index and the lowest elasticity presumably indicating skin photodamage. For most of the skin parameters, the seasonal variations probably arise due to a complex action of different factors as we extensively discussed. CONCLUSION: The data about the seasonal variations in the skin parameters are still highly inconsistent and further studies are needed for better understanding of the normal skin changes throughout the year.
- MeSH
- fyziologie kůže * MeSH
- kůže * metabolismus MeSH
- lidé MeSH
- perspiratio insensibilis MeSH
- roční období MeSH
- sebum MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Generally, skin properties are highly specific for each individual depending on various factors such as genetic predisposition, age, gender, body region, health and lifestyle. In this study, we measured various skin parameters on forehead, temple and cheek of 442 Caucasian women between 23 and 63 years, and evaluated differences between these facial regions and also the relationship between skin parameters and age of the volunteers. We measured transepidermal water loss (TEWL), stratum corneum hydration, skin gloss, melanin level, individual typology angle (ITA), erythema, sebum level and elasticity (R7). We observed significant negative relationship between age and TEWL, elasticity and skin lightness represented by ITA. Sebum, melanin and erythema levels increased up to the age of 50, when menopause usually takes place, and then decreased again. Evaluating the skin parameters on the forehead, temple and cheek area, we observed the biggest differences between the cheek and the forehead. The cheek possessed the worst skin parameters, such as the highest TEWL and erythema values and the lowest hydration.
- MeSH
- běloši MeSH
- dospělí MeSH
- epidermis metabolismus MeSH
- erytém epidemiologie MeSH
- fyziologie kůže * MeSH
- lidé středního věku MeSH
- lidé MeSH
- obličej * MeSH
- perspiratio insensibilis MeSH
- pružnost MeSH
- sebum metabolismus MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Analysis of epidermal genes, proteins and lipids is important in the research and diagnosis of skin diseases. Although punch biopsy is the first-choice technique for the skin sampling, it is unnecessarily invasive for obtaining a sample just for the epidermal analysis. Here we compare two less invasive methods, suction blistering (SB) and tape stripping (TS), for the analysis of selected epidermal genes (quantitative real-time reverse transcription PCR, qRT-PCR), proteins (western blotting, WB), and lipids in ten healthy volunteers. TS provided significantly less material than SB and no viable epidermal layers could be obtained according to the reflectance confocal microscopy. Consistently, only the SC protein filaggrin and housekeeping GAPDH together with FLG and RPL13A mRNA were detected by TS. In the SB samples, WB and qRT-PCR could easily detect all the selected proteins (claudin-1, occludin, filaggrin, laminin and GAPDH) and genes (CLDN1, OCLN, FLG, LAMA3 and RPL13A), respectively. A single SB sample further provided enough of material for immunohistochemistry and lipid analyses, which was not feasible with the TS samples. Immunohistochemistry of the SB samples showed intact epidermal structure and a characteristic expression of claudin-1. Infrared spectroscopy showed well-ordered lipids with both orthorhombic and hexagonal packing and high-performance thin layer chromatography confirmed all lipid classes (including ceramide subclasses) in correct proportions. Taken together, SB represents a reliable sampling technique that can be utilized for multipurpose epidermal analyses in various studies.
- MeSH
- chromatografie na tenké vrstvě MeSH
- claudin-1 analýza MeSH
- dospělí MeSH
- epidermis chemie MeSH
- imunohistochemie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy analýza MeSH
- messenger RNA analýza MeSH
- odsávání MeSH
- proteiny intermediálních filament analýza MeSH
- proteiny analýza MeSH
- puchýř MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
A series of 2,9-substituted 6-guanidinopurines, structurally related to the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine, has been synthesized and characterized. A new copper-catalyzed method for the synthesis of 2-substituted 6-guanidino-9-isopropylpurines under mild reaction conditions has been developed. All prepared compounds were screened for their CDK1 and CDK2 inhibitory activities, cytotoxicity and antiproliferative effects in the breast cancer-derived cell line MCF7. The most active derivative 16g possessed an identical side chain in the C2 position to roscovitine; this compound displayed approximately five fold higher inhibitory activity towards CDK2/cyclin E and more than ten fold increase in cytotoxicity in MCF7 cells. Interestingly and in contrast to previously described findings, (S)-6-guanidinopurine derivatives were generally more active than their (R)-counterparts. Kinase selectivity profiling of (R)- and (S)-enantiomers 16e and 16g, respectively, revealed that introduction of a guanidino group at the C6 position of the purine moiety decreased selectivity towards protein kinases compared to roscovitine. Nevertheless, increased inhibitory activity and decreased selectivity offer a good starting point for further development of new protein kinase inhibitors.
- MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- buněčný cyklus účinky léků MeSH
- cyklin-dependentní kinasa 2 antagonisté a inhibitory metabolismus MeSH
- guanidin analogy a deriváty chemická syntéza farmakologie MeSH
- inhibitory proteinkinas chemická syntéza chemie farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- proliferace buněk účinky léků MeSH
- proteinkinasa CDC2 antagonisté a inhibitory metabolismus MeSH
- puriny chemická syntéza chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Flavone eupatorin is one of the constituents of Orthosiphon stamineus, a medicinal herb used in folk medicine in South East Asia for treatment of various disorders. In our study, we investigated the antiproliferative properties of a chloroform extract of the leaves of O. stamineus and of pure eupatorin. The compound was able to reduce the number of viable cancer cells to the same extent as the extract, with IC(50) values in micromolar range. Moreover, both the eupatorin standard and the extract caused cells to arrest in the G2/M phase of the cell cycle. This clearly demonstrates that eupatorin contributes significantly to the overall extract activity. Induction of mitotic catastrophe, accompanied by key molecular events defining apoptosis, is the mechanism of eupatorin-induced cell death. Importantly, eupatorin (at the doses cytotoxic to cancer cells) did not kill normal cells; it only limited migration of HUVEC endothelial cells and their ability to create tubes. The ability of eupatorin to nonspecifically inhibit many protein kinases was proven and is the probable cause of its cellular effects. In summary, eupatorin emerges as a promising agent in anticancer research.
- MeSH
- antitumorózní látky fytogenní farmakologie terapeutické užití MeSH
- apoptóza účinky léků MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- flavonoidy farmakologie terapeutické užití MeSH
- flavony farmakologie terapeutické užití MeSH
- fytoterapie MeSH
- inhibiční koncentrace 50 MeSH
- inhibitory angiogeneze farmakologie terapeutické užití MeSH
- kontrolní body buněčného cyklu účinky léků MeSH
- lidé MeSH
- listy rostlin MeSH
- Orthosiphon chemie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- proteinkinasy metabolismus MeSH
- rostlinné extrakty farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH