Laser Scanning Microscopic Investigations of the Decontamination of Soot Nanoparticles from the Skin

Background/Aims: Airborne pollutants, such as nano-sized soot particles, are increasingly being released into the environment as a result of growing population densities and industrialization. They can absorb organic and metal compounds with potential biological activity, such as polycyclic aromatic hydrocarbons and airborne pollen allergens. Local and systemic toxicities may be induced in the skin if the particulates release their harmful components upon dermal contact. Methods: In the present study, skin pretreatments with serum and/or shield as barrier formulations prior to exposure and washing with a cleanser subsequent to exposure were evaluated as a protection and decontamination strategy using laser scanning microscopy. Results: The results indicate that while the application of serum and a cleanser was insufficient for decontamination, the pretreatment with shield prior to nanoparticle exposure followed by washing led to the removal of a considerable amount of the carbon black particles. The combined application of serum and shield before the administration of carbon black particles and subsequent washing led to their elimination from the skin samples. Conclusion: The application of barrier-enhancing formulations in combination with a cleanser may reduce the penetration of harmful airborne particulates by preventing their adhesion to the skin and facilitating their removal by subsequent washing with the cleanser

Post-Transcriptional Regulation of Interleukin-6 Gene Expression in Human Keratinocytes by Ultraviolet B Radiation

Exposure to increasing doses (290-315 nm) of ultraviolet (UV) B radiation is thought to profoundly affect human health. Studies on the biologic and molecular effects of UVB radiation on human skin are therefore of particular interest. There is experimental and clinical evidence to assume that UVB radiation-induced local and systemic inflammatory reactions might be mediated at least in part by UVB-induced keratinocyte-derived interleukin (IL)-6. Previously, a UVB-induced increase of steady-state levels of IL-6 mRNA was found to be a prerequisite for keratinocyte IL-6 production after UVB irradiation. The present study was aimed at addressing the question of whether in vitro UVB irradiation would increase IL-6 mRNA expression in long-term cultured, normal human keratinocytes via transcriptional or post-transcriptional mechanisms. UVB exposure (0-100 J/m2) of keratinocytes increased low baseline expression levels of lL-6 mRNA in a time- and dose-dependent manner. Using nuclear run-on assays, transcription rates of the II,-6 gene in nuclei isolated from UVB-irradiated cells were found to be essentially identical to those seen in unirradiated cells, indicating that UVB light did not lead to increased transcription of the IL-6 gene. To determine a possible post-transcriptional mechanism in UVB-induced IL-6 mRNA expression, the effects of UVB irradiation on IL-6 mRNA stability were examined. To this end irradiated and unirradiated keratinocytes were treated with actinomycin D and subjected to Northern blot analysis to calculate IL-6 mRNA half-life. As compared with unirradiated cells, IL-6 mRNA stability was increased significantly (three- to four-fold) in UVB-irradiated cells, suggesting that UVB radiation upregulates IL-6 mRNA levels in human keratinocytes by increasing the stability of IL-6 transcripts. This is the first report indicating that UVB radiation at a physiologically relevant dose may affect gene expression in human cells at a post-transcriptional level

Shedding light on the variability of optical skin properties: finding a path towards more accurate prediction of light propagation in human cutaneous compartments

YesFinding a path towards a more accurate prediction of light propagation in human skin remains an aspiration of biomedical scientists working on cutaneous applications both for diagnostic and therapeutic reasons. The objective of this study was to investigate variability of the optical properties of human skin compartments reported in literature, to explore the underlying rational of this variability and to propose a dataset of values, to better represent an in vivo case and recommend a solution towards a more accurate prediction of light propagation through cutaneous compartments. To achieve this, we undertook a novel, logical yet simple approach. We first reviewed scientific articles published between 1981 and 2013 that reported on skin optical properties, to reveal the spread in the reported quantitative values. We found variations of up to 100-fold. Then we extracted the most trust-worthy datasets guided by a rule that the spectral properties should reflect the specific biochemical composition of each of the skin layers. This resulted in the narrowing of the spread in the calculated photon densities to 6-fold. We conclude with a recommendation to use the identified most robust datasets when estimating light propagation in human skin using Monte Carlo simulations. Alternatively, otherwise follow our proposed strategy to screen any new datasets to determine their biological relevance.European Marie-Curie Actions Programme, Grant agreement no. 60788

Unraveling the interplay between senescent dermal fibroblasts and cutaneous squamous cell carcinoma cell lines at different stages of tumorigenesis

Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common type of non-melanoma skin cancer in white-skinned populations. cSCC is associated with sun exposure and aging, which is concomitant with an accumulation of senescent cells in the skin. The involvement of senescent cells in carcinogenesis has been highlighted in several cancer types and an interaction between cSCC cells and senescent cells is proposed, but still little explored. Tumor-associated effects are mostly attributed to the senescence-associated secretory phenotype (SASP). Here, we compared two in vitro models of senescence, namely replicative senescence and UVB-stress induced premature senescence (UVB-SIPS), in human dermal fibroblasts and screened for expression of SASP-related genes in our models. Next, the impact of senescent fibroblasts on three cSCC isogenic cell lines, representing different stages of keratinocyte malignant transformation, was studied. Only a limited impact on cSCC cell lines’ growth and migration has been detected with conditioned media collected from senescent fibroblasts and indirect co-cultures. We then investigated the opposite interaction and found that cSCC cell lines maintained in indirect co-cultures with fibroblasts induced and reinforced their senescence state as shown by an increased proportion of cells positive for the senescence-associated β-galactosidase activity and an increased expression of several SASP-related genes. Moreover, these effects were modulated according to the stage of tumorigenesis of the different cSCC cell lines used. Finally, cSCC cell lines-co-cultures are associated with NF-κB activation in HDFs. Understanding the interplay between tumor cells and their microenvironment may have important influences in cancer research and therapeutic strategies.</p

Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain

Combustion-derived nanoparticles, such as diesel engine exhaust particles, have been implicated in the adverse health effects of particulate air pollution. Recent studies suggest that inhaled nanoparticles may also reach and/or affect the brain. The aim of our study was to comparatively evaluate the effects of short-term diesel engine exhaust (DEE) inhalation exposure on rat brain and lung. After 4 or 18 h recovery from a 2 h nose-only exposure to DEE (1.9 mg/m(3)), the mRNA expressions of heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytochrome P450 1A1 (CYP1A1) were investigated in lung as well as in pituitary gland, hypothalamus, olfactory bulb, olfactory tubercles, cerebral cortex, and cerebellum. HO-1 protein expression in brain was investigated by immunohistochemistry and ELISA. In the lung, 4 h post-exposure, CYP1A1 and iNOS mRNA levels were increased, while 18 h post-exposure HO-1 was increased. In the pituitary at 4 h post-exposure, both CYP1A1 and HO-1 were increased; HO-1 was also elevated in the olfactory tuberculum at this time point. At 18 h post-exposure, increased expression of HO-1 and COX-2 was observed in cerebral cortex and cerebellum, respectively. Induction of HO-1 protein was not observed after DEE exposure. Bronchoalveolar lavage analysis of inflammatory cell influx, TNF-α, and IL-6 indicated that the mRNA expression changes occurred in the absence of lung inflammation. Our study shows that a single, short-term inhalation exposure to DEE triggers region-specific gene expression changes in rat brain to an extent comparable to those observed in the lung

Probiotic Bacteria Induce a ‘Glow of Health’

Radiant skin and hair are universally recognized as indications of good health. However, this ‘glow of health’ display remains poorly understood. We found that feeding of probiotic bacteria to aged mice induced integumentary changes mimicking peak health and reproductive fitness characteristic of much younger animals. Eating probiotic yogurt triggered epithelial follicular anagen-phase shift with sebocytogenesis resulting in thick lustrous fur due to a bacteria-triggered interleukin-10-dependent mechanism. Aged male animals eating probiotics exhibited increased subcuticular folliculogenesis, when compared with matched controls, yielding luxuriant fur only in probiotic-fed subjects. Female animals displayed probiotic-induced hyperacidity coinciding with shinier hair, a feature that also aligns with fertility in human females. Together these data provide insights into mammalian evolution and novel strategies for integumentary health

Galacto-Oligosaccharides : production, properties, applications, and significance as prebiotics

Galacto-oligosaccharides (GOS) have now been definitely established as prebiotic ingredients after in vitro and animal and human in vivo studies. Currently, GOS are produced by glycoside hydrolases (GH) using lactose as substrate. Converting lactose into GOS by GH results in mixtures containing GOS of different degrees of polymerization (DP), unreacted lactose, and monomeric sugars (glucose and galactose). Recent and future developments in the production of GOS aim at delivering purer and more efficient mixtures. To produce high-GOS-content mixtures, GH should not only have good ability to catalyze the transgalactosylation reaction relative to hydrolysis, but also have low affinity for the GOS formed relative to the affinity for lactose. In this article, several microbial GH, proposed for the synthesis of GOS, are hierarchized according to the referred performance indicators. In addition, strategies for process improvement are discussed. Besides the differences in purity of GOS mixtures, differences in the position of the glycosidic linkages occur, because different enzymes have different regiochemical selectivity. Depending on oligosaccharide composition, GOS products will vary in terms of prebiotic activity, as well as other physiological effects. This review focuses on GOS production from synthesis to purification processes. Physicochemical characteristics, physiological effects, and applications of these prebiotic ingredients are summarized. Regulatory aspects of GOS-containing food products are also highlighted with emphasis on the current process of health claims evaluation in Europe.Agência da Inovação-Progama IDEIA (Portugal)Fundação para a Ciência e a Tecnologia (FCT