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1.
Leslie Calapre Elin S. Gray Sandrine Kurdykowski Anthony David Pascal Descargues Mel Ziman 《BMC dermatology》2017,17(1):8
Background
Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes.Results
Activation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin.Conclusion
This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat2.
Lorena?Capriotti Biagio?Didona Stefania?Madonna Claudia?Scarponi Maria?Antonietta?Pilla Francesco?Facchiano Martina?Cordella Andrea?Cavani Cristina?Maria?Failla
Background
Eosin has been traditionally employed as a topical treatment for psoriasis, but the biological mechanism of its therapeutic action has not been fully elucidated.Objectives
To analyse eosin effects on psoriatic skin in vivo and keratinocytes and endothelial cells in vitro.Materials & Methods
Skin biopsies were taken from psoriatic plaques before and after a three-day eosin treatment and processed for histological analysis. Cultured human psoriatic keratinocytes and dermal endothelial cells were treated with eosin, and release of inflammatory chemokines was analysed by multiplexed bead-based immunoassay and ELISA.Results
In patients, the three-day eosin treatment significantly reduced the number of infiltrating T lymphocytes, neutrophilic granulocytes, and dermal dendritic cells.Areduction in VEGF-A expressionwas also observed. In vitro, eosin treatment significantly decreased the release of CCL2, CCL5, and VEGF-A by keratinocytes and angiopoietin-2 by endothelial cells.Conclusions
Eosin treatment impacts on psoriatic inflammatory infiltrates and dampens the release of proinflammatory chemokines and angiogenic factors.3.
Alanne?Rayssa?Da?Silva Melo Haline?Barroso Daniel?Uch?a De Araújo Francisco?Ruidomar Pereira Naila?Francis?Paulo?De?Oliveira
Background
Studies have shown that a variety of environmental factors and habits are associated with epigenetic changes. In addition, various genes are also found to respond to UV radiation.Objectives
The aim of this study was to investigate the sun exposure influence on the DNA methylation profile on the matrix metalloprotease-9 (MMP9), microRNA 137 (miR-137), cytokeratin 14 (KRT14) and 19 (KRT19) genes of skin cells of subjects with no history of skin diseases.Methods
Skin biopsies (5mm) were obtained using a punch technique on sun-exposed (outer forearm) and sun-protected areas (inner arm) from 30 corpses from the Brazilian Service of Death Investigation. Skin types were ranked according to Fitzpatrick’s criteria. Genomic DNA was extracted and a DNA methylation analysis was performed using Methylation Specific PCR (MSP) or Methylation-Sensitive Restriction Enzymes (MSRE) of sun-exposed and sun-protected skin areas.Results
No differences were found among the areas (p>0.05; McNemar), with the partially methylated condition found to be a common event in skin for both MMP9 and miR-137 genes and the methylated condition for both KRT14 and KRT19 genes. Additional analysis showed no differences in the methylation status when age, gender and skin type were considered, however, the methylation status of miR-137 gene seems to be genderrelated.Conclusions
We conclude that sun exposure does not induce changes in the DNA methylation status in MMP9, miR-137, KRT14 and KRT19 genes.4.
Gefei A. Zhu Inbar Raber Sukolsak Sakshuwong Shufeng Li Angela S. Li Caroline Tan Anne Lynn S. Chang 《BMC dermatology》2016,16(1):1
Background
Estimates of an individual’s cumulative ultraviolet (UV) radiation exposure can be useful since ultraviolet radiation exposure increases skin cancer risk, but a comprehensive tool that is practical for use in the clinic does not currently exist.The objective of this study is to develop a geographically-adjusted tool to systematically estimate an individual’s self-reported cumulative UV radiation exposure, investigate the association of these estimates with skin cancer diagnosis, and assess test reliability.Methods
A 12-item online questionnaire from validated survey items for UV exposure and skin cancer was administered to online volunteers across the United States and results cross-referenced with UV radiation indices. Cumulative UV exposure scores (CUES) were calculated and correlated with personal history of skin cancer in a case–control design. Reliability was assessed in a separate convenience sample.Results
1,118 responses were included in the overall sample; the mean age of respondents was 46 (standard deviation 15, range 18 – 81) and 150 (13 %) reported a history of skin cancer. In bivariate analysis of 1:2 age-matched cases (n?=?149) and controls (n?=?298), skin cancer cases were associated with (1) greater CUES prior to first skin cancer diagnosis than controls without skin cancer history (242,074 vs. 205,379, p?=?0.003) and (2) less engagement in UV protective behaviors (p?<?0.01). In a multivariate analysis of age-matched data, individuals with CUES in the lowest quartile were less likely to develop skin cancer compared to those in the highest quartile. In reliability testing among 19 volunteers, the 2-week intra-class correlation coefficient for CUES was 0.94. We have provided the programming code for this tool as well as the tool itself via open access.Conclusions
CUES is a useable and comprehensive tool to better estimate lifetime ultraviolet exposure, so that individuals with higher levels of exposure may be identified for counseling on photo-protective measures.5.
Background
Incidence of skin cancer is increasing worldwide and UV exposure at a young age is an important risk factor.Objectives
To compare sun exposure-related knowledge and behaviour among children during school and holiday periods.Material & Methods
A cross-sectional study was undertaken at 12 Oporto public primary schools. Educational sessions for educators were head by dermatologists every spring from 2004 to 2012. An educational activity book, Play and Learn with Jo Spots, was distributed to all primary school children and was explained by the educators every year. A questionnaire about sun exposure and behaviour was given to students in 2004 and 2012.Results
In total, 2,114 students answered the questionnaire (1,233 in 2004 and 881 in 2012). Children practiced more outdoor sports in 2012 than in 2004 (86% vs 56%; p<0.001), but spent less time outside when the sun’s rays were most dangerous. The use of hats (64% vs 59%; p = 0.028) and sunscreen (35% vs 15%; p<0.001) at school and the application of sunscreen before going to the beach improved over time (51% vs 26% in 2004; p<0.001). However, there was an increase in sunburn rate (43% vs 37%; p = 0.005).Conclusion
Sun exposure-related behaviour among primary school students in Oporto is improving but is still far from optimal. School would appear to be an adequate setting for effective and long-lasting sun protection interventions, and the introduction of educational books at schools, such as Play and Learn with Jo Spots, might be effective in bringing about positive behavioural changes.6.
Background
Internationally adopted children often present diseases contracted in the country of origin. Skin diseases are common in new arrivals, and diagnosis may prove challenging for GPs or even dermatologists if they are inexperienced in the extensive geographic and ethnic diversity of international adoptees.Objectives
To analyse the frequency and characteristics of skin diseases in international adoptees.Materials and Methods
In total, 142 adoptees were evaluated for a cross-sectional cohort study. The most frequent diseases observed at arrival were dermatological conditions.Results
Of the adoptees, 70% presented at least one skin disease, of which 57.5% were infectious; Tinea capitis being the most frequent (n = 42). The recovery rate of Tinea capitis was 89% (n = 32/36).Ten cases of scabies were diagnosed. Other diseases included viral skin infection (n = 22), with 16 cases of Molluscum contagiosum and bacterial infection.Conclusion
Skin diseases are very common in internationally adopted children. There is a need for close collaboration between dermatologists and paediatricians to diagnose such infections, as well as clear guidelines to treat them.7.
Background
In mammals, desynchronized circadian rhythm leads to various biological symptoms. In skin and hair, human epidermal stem cell function in vitro is regulated by circadian oscillations, and thus contributes to tissue aging when deregulated. In mice, circadian arrhythmia of hair follicle stem cells contributes to age-related hair follicle cycling defects. Despite the well-described impact of circadian oscillations through a feedback loop involving the clock pathway on hair and skin stem cell function in vitro, little is known about the change in characteristics or regenerative properties of hHF (human hair follicle keratinocytes), hEpi (human interfollicular epidermal keratinocytes), and hHFDP (hair follicle dermal papilla stem cells) after long-term alteration of circadian rhythm in vivo.Objectives
The present study was designed to asses hHF, hEpi, and hHFDP precursors and stem cell properties in response to clock pathway alteration due to long-term deregulated circadian rhythm in vivo.Materials & Methods
A clinical study protocol was designed to include two groups of women: diurnal workers (control) and shift workers (deregulated). After informed consent, two 3-mm fresh punch biopsies were taken from the occipital region of each donor (10 donors/group). Cell culture characterization, measurement of colony area, culture medium analysis, and RT-qPCR analysis were carried out.Results
Long-term circadian rhythm deregulation affected clock pathway protein expression and correlated with alterations in hHF, hEpi, and hHFDP properties.Conclusions
This study provides, for the first time in humans, evidence that in vivo deregulation of the clock pathway affects regenerative properties of human skin and hair precursor cells.8.
9.
Background
Few studies have evaluated the prevalence of skin tumours in the geriatric population and none have analysed different skin aging parameters for whole-body skin in this population.Objectives
To evaluate the prevalence of skin tumours and global skin aging in a French cohort of elderly people.Materials and methods
In total, 209 subjects, 105 women and 104 men (mean age: 77.5; range: 74-81 years), were enrolled from the PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events) cohort. SCINEXA (SCore for INtrinsic and EXtrinsic skin Aging) was used to assess the degree of skin aging and the prevalence of skin tumours. Some additional cutaneous parameters were also studied. Skin aging in women and men was compared.Results
Mean global SCINEXA was 24.3 (SD: 4.7; range: 8.2-35.3). Solar elastosis and lax appearance were more severe in women (t test; p<0.0001), whereas pseudoscars (t test; p = 0.0312) and coarse wrinkles (t test; p = 0.0479) were more severe in men. Erythrosis coli (chi-square test; p <0.0001) was more frequent in men, whereas varicous veins (chi-square test; p = 0.0026) and eyelid xanthomas (chi-square test; p = 0.0282) were more frequent in women. Twelve patients presented with cutaneous carcinomas and two patients had early melanomas.Conclusion
This research describes in detail the main indices of skin aging in an old population and the differences related to gender. Moreover, it highlights the utility of systematic screening of old patients by dermatologists in order to diagnose skin cancers early.10.
Background
Muir-Torre syndrome (MTS) is characterized by sebaceous neoplasms with internal malignancies and regarded as a variant of hereditary nonpolyposis colorectal cancer (HNPCC). Pathogenic variations of MTS have been identified in the MSH2, MLH1, and MSH6 genes, with the majority of variations located in MSH2.Objectives
To present an MTS patient who was the only individual with skin malignancies within a cancer-prone pedigree and to showthe usefulness ofRNA-based genetic analysis in the investigation of MTS.Materials & methods
A 77-year-old man who had operated X-ray equipment at his workplace in his twenties was clinically diagnosed with MTS and investigated by RNA-based analysis, multiplex ligation-dependent probe amplification, and genomic DNA sequencing.Results
The patient had suffered from sebaceous tumours, squamous cell carcinomas of the skin, and colon cancer. The patient’s family history was remarkable for visceral malignant diseases. Genetic analysis revealed homologous recombination between two Alu elements within intron 4 and 5 of the MLH1 gene. The rearrangement caused a 1,222-bp deletion, including the entire exon 5. Deletion of exon 5 has previously been reported only in two patients with HNPCC, and not in patients with MTS.Conclusions
For the genetic analysis of MTS, the possibility of rare copy number variations of MLH1, as well as MSH2 variations, should be considered. RNA-based screening using puromycin is recommended in order to identify such variations. It remains unclear why only the proband among the pedigree had skin malignancies, however, the skin carcinogenesis might have been related to occupational radiation exposure.11.
Background
Serratia marcescens is a Gram-negative, encapsulated, motile, anaerobic, non-sporulating bacillus that belongs to the Enterobacteriaceae family. It is found in water, soil, plants, food, and garbage. S. marcescens is an opportunistic pathogen. It usually causes nosocomial infections, such as lung and genitourinary infections, sinusitis, otitis, endocarditis, and sepsis. Skin infections caused by S. marcescens are rare.Objectives
To describe three new cases of skin ulcers of the leg caused by S. marcescens and review the relevant literature.Materials & methods
We investigated three patients admitted for ulcers on the leg.Results
In two patients, post-traumatic aetiology was concluded. The modality of infection was not identified for the other patient. One patient was diabetic. All patients recovered with specific antibiotic therapy (ciprofloxacin, ceftriaxone and levofloxacin, respectively).Conclusion
Skin ulcers due to S. marcescens are very rare. The three cases presented here add to the limited literature of skin infections caused by S. marcescens.12.
Background
High-throughput DNA sequencing has shown that the cutaneous microbiome varies due to different exogenous and endogenous factors.Objectives
To characterize the microbiome of cutaneous melanomas and melanocytic nevi.Material and Methods
Non-invasive swab specimens were taken from 15 cutaneous melanomas and 17 benign melanocytic nevi. Partial sequencing of the 16S ribosomal RNA gene was carried out on the 454 GS-FLX Titanium platform and the resulting sequence data was analysed by bioinformatics and statistical methods.Results
95% of the OTUs (Operational Taxonomic Units) belonged to four phyla: Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes. The genus Propionibacterium was overall the mostcommongenus, followed by Staphylococcus and Corynebacterium. Statistical analysis showed no significant differences in the relative abundances of bacterial genera or bacterial diversity between the patient groups. Melanoma samples showed a marginally decreased cutaneous microbial diversity.Conclusion
Our data suggests that the skin microbiome may not be a useful diagnostic tool for melanoma and melanocytic nevi.13.
Background
Outdoor runners have an increased risk of melanoma and non-melanoma skin cancer.Objectives
The purpose of this study was to assess skin cancer literacy and sun exposure and protection behaviour among outdoor runners during training.Materials and methods
A cross-sectional survey-based study was conducted. All athletes registered for four consecutive running events in Porto: the Porto Marathon (November 2014), the Fathers’ Day 10-km race (March 2015), the Saint John’s Day 15-km race (June 2015), and the Porto half-marathon (September 2015). Athletes were invited to answer an online survey with 23 questions on the following items: sociodemographic and constitutional factors, skin cancer literacy, and sun exposure and protection behaviour. A scoring system was devised to analyse behaviour. Multivariate analysis was performed.Results
The survey was completed by 2,445 runners, 2,159 of whom trained outdoors. Only 23.5% had adequate sun exposure and protection behaviour. A higher proportion of women than men had adequate behaviour (33% versus 17%; P < 0.001). Athletes with a university, or higher degree were more knowledgeable about skin cancer than those with a lower level of education, however, their behaviour in relation to sun exposure and protection was the same. Based on multivariate analysis, gender, skin type, marital status, and average number of hours spent training significantly affected attitude score.Conclusions
Investment in more targeted campaigns, aimed particularly at high-risk groups such as outdoor athletes, is essential to modify attitudes and behaviour regarding sun exposure and protection. Outdoor sports event organisers and sport associations also need to engage.14.
15.
Background
Clinical studies on dermal fillers have essentially focused upon visible improvement of skin quality and any eventual side effects, whereas very little is known about their detailed biological effects.Objectives
New skin equivalent models were created to investigate the biological impact of hyaluronic acid (HA) fillers on the dermal compartment in vitro.Materials and methods
Two different reconstructed skin models were developed to incorporate HA within the collagen fibers. In the mixed model, HA was distributed throughout the whole collagen gel whereas the HA was concentrated in the center of collagen gel in the inclusion model.Results
A comparison of the addition of fillers in two models of reconstructed skin has permitted a better understanding of the biological impact of HA fillers. Protein profiling of supernatants from both models suggested a regulation of MMP-1 secretion by fibroblasts as a function of HA volume, distribution in the dermis and degree of cross-linking. Immunostaining of the inclusion model revealed increased production of type I and III procollagens close to the cross-linked HA. Fibroblasts located in this area showed a fusiform morphology as well as an increase in α-smooth actin expression. The observed increase in collagen production may thus result in part from tension in fibroblasts surrounding the cross-linked HA.Conclusion
The inclusion reconstructed skin model, as compared to the mixed model, presented here, appears to be a useful tool for investigating the properties of various fillers in vitro and closer to the in vivo situation; our results show that HA fillers promote in vitro remodeling of the dermis by fibroblasts.16.
Background
Localized scleroderma (LSc) exhibits fibrosis of the skin and subcutaneous tissue. LSc shows an excessive deposition of type 1 collagen.Objectives
To elucidate the mechanism of type 1 collagen overexpression in LSc, we investigated the epigenetics, focusing on microRNA (miRNA).Materials & Methods
miRNA expression profile was determined by PCR array analysis. The expression of microRNA-196a (miR-196a) in the skin tissuewas examined by in situ hybridization or real-time PCR. The serum levels of miR-196a were measured by real-time PCR.Results
PCR array analysis demonstrated that the miR-196a level was markedly decreased in LSc skin tissue in vivo. The transfection of specific inhibitor for miR-196a into normal cultured human dermal fibroblasts led to the up-regulation of type 1 collagen protein in vitro. Furthermore, the serum levels of miR-196a were significantly decreased in LSc patients.Conclusion
Down-regulation of miR-196a and subsequent overexpression of type 1 collagen in dermal fibroblasts may play a key role in the pathogenesis of LSc. The serum levels of miR-196a may be useful as a diagnostic marker of LSc.17.
Background
Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied.Objectives
We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions.Materials and Methods
Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades.Results
In comparison to the normal skin, EZH2 expression in actinic keratosiswas increased (p = 0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001).Conclusion
EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.18.
Jung?U.?Shin Jung?Dong?Kim Hong?Kee?Kim Hong?Kyu?Kang Chulmin?Joo Ju?Hee?Lee Do?Hyeon?Jeong Seungri?Song Howard?Chu Jung?Soo?Lee Hemin?Lee Kwang?Hoon?Lee
Background
The stratum corneum is an almost impermeable barrier. Recently, microneedles have been used to increase drug delivery passing the stratum corneum by incorporating the drug within the microneedle or by coating the surface of the microneedle with the drug.Objective
This study was performed to investigate whether applying a biodegradable microneedle patch after topical steroid application increases penetration of the steroid in vitro, as well as treatment efficacy in patients with prurigo nodularis.Materials & methods
In vitro penetration of topical steroids after biodegradable microneedle patch application was measured using a 3D skin model. To evaluate the treatment efficacy of the combination of biodegradable microneedle and topical steroids, a split-body clinical study was performed.Results
Penetration of topical steroid in the in vitro skin model was significantly greater in the microneedle-applied skin. In a split-body clinical study with prurigo nodularis patients, the area and height of skin lesions decreased after four weeks of treatment on both sides, however, the microneedle patch side exhibited a significantly greater decrease in both area and height, compared to the control side. The pruritus visual analogue scale was also significantly lower on the microneedle side.Conclusion
We suggest that simply applying a microneedle patch after topical steroid application could be a useful strategy for treating refractory skin diseases such as prurigo nodularis.19.
Background
Topical administration of ketoprofen to treat local subcutaneous pain significantly reduces gastrointestinal and cardiovascular adverse effects associated with oral delivery. However, this benefit must be weighed against the risk of photosensitisation/phototoxicity.Objective
To substantiate the safety and efficacy of topical ketoprofen delivery from a patch.Methods
Experiments were performed, and published information analysed, (a) to confirm the superior skin permeability and pharmacological activity of ketoprofen, and (b) to demonstrate the lower incidence of ketoprofen photosensitisation/phototoxicity when delivered from a topical patch.Results
Ketoprofen’s photodegradation products were more photoallergic than the drug itself. The period postketoprofen treatment that skin should be protected from UV radiation (while the drug is cleared from the application site) was estimated.Conclusions
Photosensitisation to ketoprofen can be mitigated by a patch formulation, which protects the drug from direct UV exposure during skin application, and reduces the formation of even more photoallergic photodegradation products.20.