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Nickel/α-diimine catalytic systems are known for their outstanding activity in α-olefin polymerization. Polymer microstructure control is a special feature of these catalysts. However, homogeneous nickel catalysts lack competitiveness against the conventional heterogeneous catalysts, which are suitable for current industrial processes. In this regard, attaching these catalysts to a convenient carrier is a critical step. In this work, a new functionalized nickel catalytic precursor was developed, which was attached to a mesoporous silica (MCM-41). The precursor was attached either alone (single precursor) or together with a second catalyst (forming a binary precursor). This binary system aggregates the characteristics of two polymers in one product. The binary precursor presented good behavior in the ethylene polymerization reaction and catalytic activity up to 3876 kg PE mol Ni−1 h−1. The single precursors reached activities of 3964 kg PE mol Ni−1 h−1. The dual behavior was proven by the employed characterization techniques.

Atopic dermatitis is a chronic relapsing inflammatory skin disease affecting 15-20% children and 2-10% adults worldwide. Topical treatments include corticosteroids and calcineurin inhibitors, despite frequently observed adverse events such as skin atrophy, itching and burning sensations. Good alternatives that can prolong disease relief in between flare-ups are therefore needed. We conducted a randomized, single-blind, placebo-controlled, multicenter clinical trial in a Caucasian cohort of 90 children and 144 adults with mild-to-moderate atopic dermatitis that applied tested products twice daily for 60 days. A natural active from Ophiopogon japonicus, that improves atopic dermatitis symptoms in vivo, was successful in reducing the SCORing of Atopic Dermatitis (SCORAD), including erythema, pruritus and body surface area in both cohorts. The active also improved patient's quality of life and significantly reduced the number of patients relapsing compared to placebo. We conclude that this treatment could be an effective solution to help control the disease in between flare-ups.

Dermal papilla cells (DPCs) play a pivotal role in the regulation of hair follicle (HF) growth, formation, and cycling, mainly through paracrine mechanisms. In the last decade, extracellular vesicles (EVs) have been recognized as a new paracrine mechanism that can modify the physiological state of recipient cells by transferring biological material. Herein, we investigated the effect of EVs isolated from stimulated human dermal fibroblasts (DFs) on DPC activation and HF growth. We found that these EVs (st-EVs) enhanced HF growth ex vivo. Comparative transcriptomic analysis on DPCs identified specific activation of the NDP gene, encoding the non-Wnt ligand Norrin. We found that Norrin was secreted by st-EVs-stimulated DPCs activating in a noncell autonomous manner β-catenin pathway in follicular keratinocytes (human HF keratinocyte [HHFK]) and hair growth ex vivo. Although Norrin-specific receptor Frizzled4 was barely detected in HHFK, we found its presence in DF-EVs. Accordingly, DF-EVs provided Frizzled4 to potentiate Norrin effects ex vivo. Our study identifies DF-EVs as efficient activators of DPCs and Norrin as a novel modulatory player in HF physiopathology. Stem Cells 2019;37:1166–1175

Objective Although xerosis is a common skin disorder among the population, there is no in vivo global study focusing on xerotic skin. Hence, the objective of this study was to characterize xerotic skin from the surface to the molecular scale with in vivo and non-invasive approaches. Methods For this purpose, 15 healthy volunteers with normal skin and 19 healthy volunteers with xerotic skin were selected by a dermatologist, thanks to a visual scorage. Firstly, the skin surface was characterized with biometric measurements. Then, the state of skin dryness was assessed by in vivo confocal microscopy. The molecular signature of xerotic skin was then determined by in vivo confocal Raman microspectroscopy. Finally, an identification of stratum corneum (SC) lipids was performed using Normal phase liquid chromatography (NP-LC) coupled to two detectors: Corona and High Resolution/Mass Spectroscopy (HR/MS). Results Results obtained at the skin surface displayed an increase in the transepidermal water loss (TEWL) and a decrease in the hydration rate in xerotic skin. Confocal microscopy revealed an alteration of the cell shape in xerotic skin. Moreover, confocal Raman microspectroscopy demonstrated directly in vivo and non-invasively the lack of organization and conformation of lipids in this skin. Finally, HPLC analyses revealed that the three ceramide sub-classes (NdS, NS and EOP) significantly decrease in xerosis. Altogether, these results identify parameters for the characterization of xerotic skin compared to normal. Conclusion This study highlighted discriminative parameters from the surface to the molecular level in vivo and non-invasively between xerotic and normal skins. These results will be useful for the development of new cosmetic active ingredients dedicated to xerotic skin.

International audience; Aims : The objective of our study was to compare the microbiota diversity between two different age groups of Western European women. Methods and Results : Skin‐swab samples were collected directly on the forehead of 34 healthy Western European women: 17 younger (21‐31 years old) and 17 older individuals (54‐69 years old). Bacterial communities were evaluated using the 16S rRNA gene sequencing. Data revealed a higher alpha diversity on the skin of older individuals compared with younger ones. Overall microbiota structure was different between the two age groups, as demonstrated by beta diversity analysis, which also highlighted a high interpersonal variation within older individuals. Furthermore, taxonomic composition analysis showed both an increase in Proteobacteria and a decrease in Actinobacteria on the older skin. At the genus level, older skin exhibited a significant increase in Corynebacterium and a decrease in Propionibacterium relative abundance. Conclusions : Our study revealed a shift in the distribution of skin microbiota during chronological aging in Western European women. Significance and Impact of Study: Altogether these results could become the basis to develop new approaches aiming to rebalance the skin microbiota, which is modified during the aging process.

Introduction Peptide C (PC) contient des peptides, 10 % de vitamine C, de l’acide hyaluronique et de l’eau volcanique mineralisante de Vichy. Propose dans des ampoules unidose, sa formule minimaliste, grâce a son pH bas, ne necessite aucun conservateur et permet une biodisponibilite optimisee de la vitamine C. Nous avons evalue l’activite anti-oxydante de PC, sa capacite a proteger la viabilite des cellules soumises a un stress oxydatif et a stimuler la synthese de collagene, et son efficacite clinique. Materiel et methodes Des etudes in vitro ont ete realisees sur des cellules en culture (keratinocytes, ou keratinocytes et fibroblastes) et un modele de peau humaine reconstruite. Trois etudes cliniques ont ete realisees. Dans la premiere, des patches de chlorure de dansyle ont ete appliques sur les avant-bras des sujets pendant 24 h puis PC a ete applique une fois par jour sur l’un des avant-bras pendant 21 jours. La fluorescence a ete evaluee tous les jours sur les deux avant-bras. Dans la seconde, PC a ete applique une fois par jour sur le visage puis les investigateurs ont evalue la severite des rides a J0 et J28 a l’aide de l’Atlas Visuel Dynamique, et les sujets ont complete un questionnaire. Dans la troisieme etude, le nombre de rides a ete evalue apres 30 jours d’application de PC en utilisant une evaluation instrumentale de projection de franges en 3D. Resultats Au total, 32 sujets adultes ont participe a l’etude clinique no 1 ; 40 sujets ont ete evalues cliniquement dans l’etude no 2 et 47 ont complete un questionnaire ; 40 sujets ont participe a l’etude no 3. Etudes in vitro : elles ont confirme une forte action anti-oxydante, un effet protecteur significatif, avec augmentation de la viabilite des cellules soumises a un stress oxydatif, et une neosynthese de collagene. Etudes cliniques : le renouvellement cellulaire etait plus rapide (17,1 contre 19, 2 jours) avec PC. La valeur moyenne de la fluorescence apres 22 jours d’application de PC etait inferieure a celle observee pour la peau non traitee (59,6 vs 64,9 ; p Discussion Les etudes in vitro ont permis de mieux comprendre le mode d’action de PC et ont confirme sa forte activite anti-oxydante, son effet protecteur au niveau des cellules exposees a un stress oxydatif, et sa capacite a stimuler la neosynthese du collagene. Les etudes cliniques ont permis de demontrer que PC a le potentiel d’ameliorer les rides faciales et l’eclat du visage.

Atopic dermatitis (AD) is the most common skin inflammatory disease, affecting up to 3% of adults and 20% of children. Skin barrier impairment is thought to be the primary factor in this disease. Currently, there is no method proposed to monitor non-invasively the different molecular disorders involved in the upper layer of AD skin. Raman microspectroscopy has proved to be a powerful tool to characterize some AD molecular descriptors such as lipid content, global hydration level, filaggrin and its derivatives. Our investigations aimed to extend the use of in vivo Raman microspectroscopy as a rapid and non-invasive diagnostic technique for lipid conformation and organization, protein secondary structure and bound water content analysis in atopic skin. Our approach was based on the analysis of Raman data collected on the stratum corneum (SC) of 11 healthy and 10 mild-to-moderate atopic patients. Atopic skin revealed a modification of lipid organization and conformation in addition to the decrease of the lipid-to-protein ratio. This study also highlighted a reduction of the bound water and an increase in protein organized secondary structure in atopic skin. All these descriptors worsen the barrier function, state and appearance of the skin in AD. This precise and relevant information will allow an in vivo follow-up of the pathology and a better evaluation of the pharmacological activity of therapeutic molecules for the treatment of AD.

Introduction Bien que cette pathologie soit mondialement repandue, la prevalence de la dermatite atopique est particulierement importante en Asie. Le developpement de nouvelles solutions naturelles, basees sur la medecine traditionnelle chinoise, est une alternative interessante aux corticoides en dermatologie, afin de diminuer l’intensite et la frequence des crises, sans effets secondaires. Apres avoir publie l’efficacite d’oligosaccharides issus d’Ophiopogon japonicus, en relais d’un traitement par corticotherapie chez des sujets caucasiens atopiques, notre objectif ici est d’evaluer l’efficacite de ces molecules chez des patients asiatiques. Materiel et methodes Soixante-seize sujets de sexe feminin et masculin, asiatiques, d’âge compris entre 16 et 62 ans (âge moyen 39 ans), presentant une dermatite atopique en crise d’intensite legere a moderee et necessitant un traitement medicamenteux par corticotherapie ont ete selectionnes par les dermatologues du General Hospital of Air Force (Pekin, Chine). Des le debut de la phase de remission, le produit (c.-a-d. oligosaccharides issus d’O. japonicus) formule a 0,5 % en creme et le placebo ont ete appliques sur l’ensemble du corps (zones saines et atteintes), matin et soir pendant 60 jours ( Fig. 1 ). Observations L’efficacite clinique du traitement a ete evaluee selon differents criteres : – SCORAD et appreciation globale par les dermatologues ; – qualite de vie (QDV) et appreciation globale par les sujets ; – taux de rechute. Resultats Le SCORAD a diminue de 76 % suite a l’utilisation du produit alors qu’il etait reduit de seulement 56 % pour le groupe placebo (p De meme, la QDV des sujets a egalement ete significativement amelioree apres traitement avec le produit (p Bien que les differences soient significatives uniquement pour l’effet hydratant, les appreciations globales attribuees par les dermatologues et par les patients pour chaque item evalue tendent a etre meilleures pour le groupe ayant utilise le produit, comparativement au placebo. Enfin, le taux de rechute avec la formule contenant l’O. japonicus est reduit de plus de moitie en comparaison a l’utilisation de la formule placebo,11 % versus 32 % respectivement ( Fig. 2 ). Discussion La diminution significative du SCORAD et les appreciations globales revelent que les oligosaccharides issus de l’O. japonicus presentent une action hydratante et de bonnes performances therapeutiques dans le soin de la dermatite atopique chez l’adulte asiatique. De plus, la diminution du taux de rechute valide l’interet d’un soin en topique contenant ces molecules naturelles, disponibles sans conservateurs, afin de maintenir la phase de remission en relais d’un traitement medicamenteux.

International audience

Introduction L’objectif de nos travaux a ete de developper un actif naturel, parfaitement tolere, prenant en charge les symptomes de l’acne de la femme adulte. En travaillant sur la diversite moleculaire liee a l’etat de maturite des ecorces de grenade, nous avons mis au point un complexe moleculaire presentant une action transversale sur les 4 composantes physiopathologiques de l’acne (seborrhee, activite de Cutibacterium acnes, hyperkeratinisation, inflammation). L’interet des ellagitannins – punicalagine et derives, punicaline, derives d’HHDP (acide hexahydroxydiphenique) et acide ellagique – contenus dans l’actif pour le traitement de l’acne a ete cliniquement valide. Materiel et methodes Une etude multicentrique encadree par 12 dermatologues a ete realisee sur 92 femmes caucasiennes, d’âge compris entre 25 et 48 ans, presentant une acne legere a moderee necessitant la mise en place d’un traitement. Le produit (ellagitannins issus de Punica granatum) formule a 0,5 % et le placebo ont ete appliques sur le visage matin et soir pendant 30 jours. Observations : l’efficacite clinique du traitement a ete evaluee via un score clinique de la gravite de l’acne (score GEA) complete par une appreciation globale par le dermatologue et un questionnaire de qualite de vie (Acne-QoL) complete par une evaluation de l’appreciation globale par les sujets. Une analyse de la tolerance des produits a ete realisee tout au long de l’etude. Resultats Dans les conditions de l’etude, aucun effet indesirable n’a ete observe. Le produit a ete parfaitement tolere par 91 % des sujets. Le groupe ayant utilise la formule contenant le produit a obtenu des performances plus favorables que le groupe placebo : reduction du nombre total de lesions (inflammatoires et retentionnelles) de 43,9 % contre 34 % pour le placebo et reduction du score de gravite de l’acne de 26,4 % contre 17,0 % pour le placebo. L’appreciation des dermatologues est globalement plus favorable pour la formule contenant le produit que pour le placebo. Enfin, les sujets ayant utilise la formule contenant le produit ont rapporte une amelioration des indices de qualite de vie ainsi qu’une meilleure perception de l’efficacite par rapport au groupe placebo. Discussion 100 % des items cliniques, de qualite de vie et d’appreciation globale de l’efficacite par le dermatologue et le sujet sont en faveur du groupe produit et montrent ainsi l’interet des ellagitannins specifiquement extraits de l’ecorce de grenade immature dans le soin des peaux acneiques adultes. Grâce a son action transversale sur les 4 composantes fondamentales de l’acne, notre complexe moleculaire ameliore les symptomes de la pathologie en seulement 30 jours, prouvant que le produit est un soin alliant rapidite d’action et efficacite.

A new strategy is presented to obtain an efficient heterogeneous gold catalyst constituted by isolated ionic gold sites, which is known to be effective in alkyne coupling reaction. The procedure is based on a significant difference between offered gold amount and available adsorbent sites on the support, ensuring the formation of very active isolated gold ion sites. In order to achieve this purpose, mesoporous silica xerogel was grafted with an ionic silsesquioxane containing charged ammonium quaternary group. The modified silica showed 0.25 mmol of cationic sites per gram of material and presented thermal stability up to 200 °C. This material was applied as support for immobilization of Au(III) ions as square planar AuCl4− complex. The gold amount offered was just 12 % of the exchangeable capacity. The catalyst was efficiently applied in the cross coupling reactions, in which only 0.22 mol% was applied to obtain symmetric and non-symmetric 1,3-diynes.

Cell-to-cell communication in skin participates to the maintenance of homeostatic responses to foreign substances. Certain strains of Staphylococcus (S) aureus are vicious pathogens that cause deleterious effects in host cells and tissues. Both secreted toxins and structural components of S.aureus trigger an immune response, though how S.aureus stimulates host immune responses is poorly understood. We explored here how keratinocytes and fibroblasts initiate the first steps of an immune response by activating dendritic cells (DCs) through recognition of structural components of S.aureus. We treated monocyte-derived Langerhans cells (moLCs) and monocyte-derived DCs (moDCs) with conditioned media from keratinocytes (K-CM) and fibroblasts (F-CM) treated with heat-killed S.aureus (HKSA) respectively, or directly with HKSA. Immune and inflammatory responses from keratinocytes, fibroblasts, moLCs and moDCs were assessed by analysis of cell surface markers and cytokine production using flow cytometry, real-time PCR and ELISA assays. K-CM and F-CM increased the expression of CD86 and HLA-DR on moLCs and moDCs, in association with a specific cytokine profile. K-CM upregulated TNFA, IL-1B and GM-CSF mRNA expression in moLCs, while F-CM upregulated IL-12 and downregulated TNFA and TGFB mRNA expression in moDCs. Additionally, F-CM attenuated the induction of an inflammatory profile in monocytes. The recognition of structural components from S.aureus by cutaneous microenvironment induces the activation and the expression of specific cytokines from LCs and DCs.

International audience; In this paper, we propose methods to extract texture features from multispectral skin images. We first describe the acquisition protocol and corrections we applied on multispectral skin images. In the framework of a cosmetology application, a skin morphological texture evaluation is then proposed using either multivariate approach on multispectral dataset or marginal on a dataset whose dimensionality has been reduced by a multivariate analysis based on PCA.

During the aging process, the human skin suffers many alterations including dryness, skin barrier function damage. The skin barrier function is important to the prevention of skin alterations and maintenance of homeostasis. So, the objective of this study was to assess the clinical efficacy on skin barrier function of Cichorium intybus root extract in cosmetic formulations with or without UV filters. Fifty women, aged between 45 and 60 years, were divided into two groups. One group received vehicle formulations containing UV filters, and the other group received formulations without UV filters. Both groups received a formulation containing the extract and the vehicle. The formulations were applied twice daily to the upper arms after washing with sodium lauryl sulphate. Transepidermal water loss (TEWL) and skin microrelief were evaluated before and after a 14- and 28-day period of treatment. The control regions and regions where the vehicles were applied showed an increase in the TEWL. For the formulations containing the extract, decreased TEWL and improved microrelief were observed when compared to the vehicle and control areas after a 28-day period. In conclusion, Cichorium intybus root extract showed protective and restructuring effects on the skin and stands out as an innovative ingredient to improve skin barrier function.

Principal Component Analysis (PCA) is a technique of multivariate data analysis widely used in various fields like biology, ecology or economy to reduce data dimensionality while retaining most important information. It is becoming a standard practice in multispectral/hyperspectral imaging since those multivariate data generally suffer from a high redundancy level. Nevertheless, by definition, PCA is meant to be applied to a single multispectral/hyperspectral image at a time. When several images have to be treated, running a PCA on each image would generate specific reduced spaces, which is not suitable for comparison between results. Thus, we focus on two PCA based algorithms that could define common reduced spaces of representation. The first method arises from literature and is computed with the barycenter covariance matrix. On the contrary, we designed the second algorithm with the idea of correcting standard PCA using permutations and inversions of eigenvectors. These dimensionality reduction methods are used within the context of a cosmetological study of a foundation make-up. Available data are in-vivo multispectral images of skin acquired on different volunteers in time series. The main purpose of this study is to characterize the make-up degradation especially in terms of texture analysis. Results have to be validate by statistical prediction of time since applying the product. PCA algorithms produce eigenimages that separately enhance skin components (pores, radiance, vessels...). From these eigenimages, we extract morphological texture descriptors and intent a time prediction. Accuracy of common reduced spaces outperform classical PCA one. In this paper, we detail how PCA is extended to the multiple groups case and explain what are the advantages of common reduced spaces when it comes to study several multispectral images.

International audience

Summary Background Atopic dermatitis (AD) is a chronic inflammatory skin disease in which skin barrier function is disrupted. In this AD environment, proinflammatory cytokines are upregulated, promoting a vicious circle of inflammation. Although several three-dimensional in vitro models mimicking AD have been published, no study has presented a fully characterized and controlled model of AD-related inflammation. Objectives To develop and characterize, from the morphological to the molecular level, a compromised reconstructed epidermis (RE) mimicking AD-related inflammation in vitro. Methods Normal human keratinocytes were used to generate RE, treated or not with an inflammatory cocktail (polyinosinic–polycytidylic acid, tumour necrosis factor-α, interleukin-4 and interleukin-13). Results The inflammatory cocktail induces some modifications observed in patients with AD: (i) it leads to spongiosis; (ii) it alters early and terminal differentiation proteins; (iii) it increases thymic stromal lymphopoietin and interleukin-8 secretion by keratinocytes and (iv) it results in a specific gene expression pattern. Conclusions The inflammatory context contributes to the morphological, functional and transcriptomic changes observed in AD skin. As a result, this compromised RE model shares some characteristics with those found in AD skin and thus can be used as a relevant tool for screening formulations and drugs for the treatment of AD.

Introduction La pemphigoide bulleuse est la dermatose bulleuse auto-immune la plus frequente. Son incidence en France est estimee a 21,7 nouveaux cas par an par million d’habitants. Le traitement de reference est la corticotherapie locale a forte dose. La cascade inflammatoire joue un role essentiel dans le processus lesionnel mais la place des differentes cytokines reste a definir. Materiel et methodes Une etude retrospective avait pour but d’etudier l’expression de l’IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, TNF-alpha, INF-gamma dans le serum des patients atteints de pemphigoide bulleuse. Elle portait sur 66 cas de pemphigoide bulleuse (PB) et 35 cas de pemphigoide cicatricielle (PC). L’objectif secondaire cherchait une correlation entre l’expression de ces cytokines et une presentation clinique ou un profil immunologique particulier ainsi que l’expression de ces memes cytokines dans la pemphigoide cicatricielle. Les taux d’IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, TNF-alpha, et INF-gamma par cytometrie de flux etaient mesures. Resultats La moyenne des taux d’IL-6 dans le groupe des patients atteints de PB etait de 22,23 pg/mL et celle des controles etait de 4,21 pg/mL. Le taux d’IL-6 dans le serum des patients etait significativement superieur a celui de la population controle (p = 0,0146). Parmi les sous groupes etudies, la moyenne des taux d’IL-6 des patients ayant des formes severes de PB avec des taux d’anticorps anti-BP180 > 200 etait significativement augmentee (p = 0,0029) contrairement au sous groupe ayant une forme peu severe de PB (p = 0,3397). Les taux d’IL-10, IL-17A, IL-17F, IL-21, IL-22, TNF-alpha, INF-gamma n’etaient pas augmentes. Il n’y avait pas d’augmentation des differentes cytokines etudiees dans le groupe des patients atteints de pemphigoide cicatricielle. Discussion Il semble que l’IL-6 joue un role important dans la cascade inflammatoire de la PB. Le taux d’IL-6 semble egalement correle a la severite de la pemphigoide bulleuse. Ce constat nous permet d’envisager un traitement par anti-IL-6 dans les cas severes de PB. Conclusion L’IL-6 est augmentee de maniere significative dans le serum des patients atteints de formes severes PB.

Among matrix proteins, fibronectin (Fn) has been known to adhesion protein containing binding site to extracellular matrix proteins (collagen, fibulin) and cell surface receptor (integrin). Although the expression of MMP by fibronectin fragments (Fn-frs) have been investigated in chondrocyte, little is known about the roles of Fn-frs in aged human skin and normal human fibroblasts (NHFs), and the roles of cathepsin G that digested Fn. Therefore, the purpose of this study was to investigate the relationship between cathepsin G-mediated fragmentation of Fn and induction of MMPs that leads to increased extracellular matrix degradation during intrinsic aging and photoaging in skin.Fn-frs were measured in young and aged skin, and then compared with cathepsin G. We also investigated whether Fn-frs increase MMP-1 expression and cathepsin G stimulate proMMP-1 to convert active MMP-1. We found that cathepsin G expression is higher in aged skin than in young skin, and that this is correlated with increased fragmentation of Fn. Studies with cultured normal human fibroblasts (NHFs) showed that specific Fn fragments (Fn-f45:N-terminal gelatin binding fragment, Fn-f70:N-terminal heparin and gelatin binding fragment) induced MMP-1 expression and MMP-2 activity.Thus, the generation of Fn fragments by cathepsin G contributes to damage of matrix in aged skin.