Pigmentation effects of blue light irradiation on skin and how to protect against them.

BACKGROUND: Visible light, in particular blue light, has been identified as an additional contributor to cutaneous photoageing. However, clinical studies demonstrating the clear effect of blue light on photoageing are still scarce, and so far, most studies have focused on broad-spectrum visible light. Although there is evidence for increased skin pigmentation, the underlying mechanisms of photoageing in vivo are still unclear. Furthermore, there is still a need for active ingredients to significantly protect against blue light-induced hyperpigmentation in vivo. Our study had two aims: to detect visible changes in skin pigmentation following repeated irradiation of the skin with LED-based blue light and to reduce pigmentation using suitable active ingredients. METHOD: We conducted a randomized, double-blind and placebo-controlled clinical study on 33 female volunteers with skin phototypes III and IV. We used a repetitive blue light (4 × 60 J cm-2 , 450 nm) irradiation protocol on the volunteers' inner forearms. Using hyperspectral imaging, we assessed chromophore status. In addition, we took chromameter measurements and photographs to assess visible hyperpigmentation. RESULTS: We measured significant changes in chromophore status (P < 0.001 vs baseline), that is of melanin, haemoglobin and oxygen saturation, immediately after blue light irradiation. In addition, we found visible skin colour changes which were expressed by a significant decrease in ITA° values (delta ITA° = -16.89, P < 0.001 vs baseline for the placebo group) and an increase in a* (delta a* = +3.37, P < 0.001 vs baseline for the placebo group) 24 h post-irradiation. Hyperpigmentation and skin reddening were mitigated by both a formulation containing 3% of a microalgal product and a formulation containing 3% niacinamide. CONCLUSION: Our study sets out an efficient and robust protocol for investigating both blue light-induced cutaneous alterations, such as changes in skin chromophores, and signs of photoageing, such as hyperpigmentation. Moreover, we have shown evidence that both an extract of the microalga Scenedesmus rubescens and niacinamide (vitamin B3) have the potential to protect against blue light-induced hyperpigmentation.

CONTEXTE: La lumière visible, en particulier la lumière bleue, a été identifiée comme un facteur supplémentaire du photo-vieillissement cutané. Cependant, les études cliniques, démontrant l'effet réel de la lumière bleue sur le photo-vieillissement, sont encore rares et jusqu'à présent, la plupart des études portaient sur l'influence de la lumière visible à large spectre. Bien qu'il y ait des preuves concernant l'effet sur la pigmentation de peau, les mécanismes sous-jacents du photo-vieillissement in vivo sont encore peu clairs. De plus, le besoin d'ingrédients actifs protégeant de manière significative en in vivo contre l'hyperpigmentation induite par la lumière bleu est toujours présent. NOTRE ÉTUDE A EU DEUX OBJECTIFS: Détecter des changements visibles dans la pigmentation de la peau à la suite d'une irradiation répétée avec de la lumière bleue à base de LED, et réduire la pigmentation à l'aide d'ingrédients actifs adaptés. MÉTHODE: Nous avons mené une étude clinique randomisée, à l'aveugle et controlée avec un placebo sur 33 volontaires féminins de phototypes de peau III et IV. Nous avons défini un protocole d'irradiation répétitif à lumière bleue (4 x 60 J cm-2, 450 nm) sur les avant-bras intérieurs des volontaires. En utilisant l'imagerie hyperspectrale nous avons évalué l'état de chromophore. En outre, nous avons pris des mesures de couleur et des photographies pour évaluer l'hyperpigmentation de manière visuelle. RÉSULTATS: Nous avons mesuré des changements significatifs dans le statut de chromophore (p<0.001 par rapport au statut initial), par exemple au niveau de la mélanine, de l'hémoglobine et de la saturation en oxygène, immédiatement après l'irradiation à lumière bleue. De plus, nous avons constaté des changements visibles de couleur de la peau qui ont été exprimés par une diminution significative des valeurs ITA° (delta ITA° valeurs = -16.89, p<0.001 par rapport au statut initial pour le groupe placebo), et une augmentation de a* (delta a* = +3.37, p <0.001 par rapport au statut initial pour le groupe placebo) 24 heures après l'irradiation. L'hyperpigmentation et les rougeurs de la peau ont été atténués par une formulation contenant 3% d'un extrait d'algue ainsi que par une formulation contenant 3% de niacinamide. CONCLUSION: Notre étude a établi un protocole efficace et robuste pour étudier à la fois les altérations cutanées induites par la lumière bleue, telles que les changements dans les chromophores de la peau, ainsi que les signes de photo-vieillissement, tels que l'hyperpigmentation. Enfin, nous avons prouvé qu'un extrait de l'algue Scenedesmus rubescens et la niacinamide (vitamine B3) avaient le potentiel de protéger contre l'hyperpigmentation induite par la lumière bleue.

Revealing the secret life of skin - with the microbiome you never walk alone.

The human skin microbiome has recently become a focus for both the dermatological and cosmetic fields. Understanding the skin microbiota, that is the collection of vital microorganisms living on our skin, and how to maintain its delicate balance is an essential step to gain insight into the mechanisms responsible for healthy skin and its appearance. Imbalances in the skin microbiota composition (dysbiosis) are associated with several skin conditions, either pathological such as eczema, acne, allergies or dandruff or non-pathological such as sensitive skin, irritated skin or dry skin. Therefore, the development of approaches which preserve or restore the natural, individual balance of the microbiota represents a novel target not only for dermatologists but also for skincare applications. This review gives an overview on the current knowledge on the skin microbiome, the currently available sampling and analysis techniques as well as a description of current approaches undertaken in the skincare segment to help restoring and balancing the structure and functionality of the skin microbiota.

Le microbiome de la peau humaine est récemment devenu un centre d'intérêt pour les domaines dermatologique et cosmétique. Comprendre le microbiote cutané, à savoir la collection de microorganismes vitaux vivant sur notre peau, et comment maintenir son équilibre délicat est une étape essentielle pour mieux comprendre les mécanismes responsables d'une peau saine et son apparence. Les déséquilibres dans la composition microbiotique de la peau (dysbiose) sont associés à plusieurs affections cutanées, soit pathologiques comme l'eczéma, l'acné, les allergies ou les pellicules, soit non pathologiques comme la peau sensible, irritée ou sèche. Par conséquent, le développement d'approches qui préservent ou restaurent l'équilibre naturel et individuel du microbiote représente une nouvelle cible non seulement pour les dermatologues mais aussi pour les experts en cosmétiques. Cette revue donne un aperçu des connaissances actuelles sur le microbiome cutané, les techniques d'échantillonnage et d'analyse actuellement disponibles ainsi qu'une description des approches actuelles entreprises dans le segment des soins de la peau pour aider à restaurer et équilibrer la structure et la fonctionnalité du microbiote de la peau.

The effects of benzylsulfonyl-D-Ser-homoPhe-(4-amidino-benzylamide), a dual plasmin and urokinase inhibitor, on facial skin barrier function in subjects with sensitive skin.

OBJECTIVE: The aim of this study was to optimize the synthesis of the plasmin and urokinase (uPA) inhibitor benzylsulfonyl-D-Ser-homoPhe-(4-amidino-benzylamide) (BSFAB), to characterize its activity and mechanism of action and to assess its use to improve stratum corneum (SC) barrier function. METHODS: Peptide coupling methods were used to synthesize BSFAB, and high-performance liquid chromatography-mass spectrometry (HPLC-MS) together with 1 H- and 13 C-nuclear magnetic resonance spectroscopy (NMR) were applied to clarify its structure and determine its purity. Its binding mode was determined by docking studies to the catalytic domains of plasmin and uPA. Inhibition constants (Ki ) were determined by enzyme kinetic studies, and the effect of BSFAB on plasmin, uPA and transglutaminase 1 expression was evaluated in non-cytokine and cytokine-stimulated keratinocytes. A vehicle-controlled clinical study on SC barrier function was conducted on facial skin of subjects with self-perceived sensitive skin. RESULTS: BSFAB was synthesized with high purity (97.3%). In silico studies indicated that the amidine moiety of BSFAB was anchored in the S1 pocket of both enzymes by binding to Asp189, Ser190 and Gly219, whereas the backbone of the D-Ser residue makes an anti-parallel ß-sheet interaction with Gly216. BSFAB was shown to be an effective inhibitor of plasmin and uPA with Ki values of 29 and 25 nM, respectively. BSFAB also inhibited keratinocyte-secreted protease activities in basal (plasmin inhibition 37.7%, P < 0.05 and uPA inhibition 96.6%, P < 0.01) and cytokine-induced conditions (plasmin inhibition 41.1%, P < 0.05 and uPA inhibition 97.0%, P < 0.001) and stimulated the gene expression of transglutaminase 1 in cytokine-stimulated keratinocytes (approximately 4.5 times increased expression, P < 0.01). Clinically, BSFAB was shown to improve SC barrier integrity (P < 0.02 on day 29) and subjective improvements in the perception of healthy skin (P < 0.05 on day 28). CONCLUSION: BSFAB binds as a reversible competitive inhibitor to the active sites of plasmin and uPA. Additionally, BSFAB positively improved keratinocyte differentiation gene expression (transglutaminase 1). These effects were translated into improvements in SC barrier integrity clinically in subjects with dry and sensitive skin and improved their perception of having a healthy skin condition.

Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency.

There is an increasing interest in the role of coagulation factor XIII (FXIII) in cardio- and cerebrovascular diseases. It has recently been reported that a common G-->T point mutation in the A-subunit gene of FXIII, which codes for a valine (val) to leucine (leu) change (FXIIIVal34Leu), is protective against thrombotic diseases but seems to increase the risk of intracerebral bleeding. We developed a colorimetric incorporation assay for detection of FXIII activity based on incorporation of 5-(biotinamido) pentylamine (BAPA) into fibrin or fibrinogen. With this new assay, we studied the effects of FXIIIVal34Leu mutation, plasma fibrinogen concentration and congenital FXIII deficiency on FXIII activity. There are no data available about the ability of different FXIII assays to detect altered activity in FXIIIVal34Leu genotypes. We therefore compared our results determined by the incorporation method with a commonly used photometric method based on ammonia release after cross-linking of glycine-ethylester to a specific glutamine containing peptide substrate. We also determined FXIII A-subunit antigen (Ag) levels using enzyme-linked immunosorbent assay (ELISA) technique. The FXIIIVal34Leu genotype could not be detected either by the photometric method nor by the FXIII A-subunit ELISA. The incorporation assay showed an increased specific FXIII activity in subjects possessing the leu allele. The photometric assay and ELISA gave similar results independent from genotype. In patients with congenital FXIII deficiency before and after substitution, however, ELISA and the incorporation assay gave similar results, whereas the photometric assay showed consistently higher values. Our results show that the incorporation assay, not the photometric assay based on ammonia release, can be used for detection of elevated activity in subjects with FXIIIVal34Leu. Because of specificity and over a wide range sensitivity, the assay can also be used for determination of FXIII deficiency and monitoring of FXIII substitution therapy.