Influence of cosmetic formulations on the skin's circadian clock.

OBJECTIVE: The circadian rhythm was set into focus by awarding the Nobel Price of Physiology/Medicine to Jeffrey Hall, Michael Rosbash and Michael Young in late 2017. Numerous publications elucidated the molecular mechanisms driving the circadian biorhythms of our body, peripheral organs and each single cell. However, there is minor knowledge on the circadian rhythm of the skin, which has its own peripheral circadian clock in contact with cosmetic formulations. The skin's epidermal clock is excessively influenced by environmental factors like UV radiation or modern lifestyle, which may induce epidermal jetlag. Here, we give an overview on the current knowledge about the epidermal circadian clock and provide a cosmetic solution to protect and preserve the biorhythm of the skin. METHODS: Quantitative RT-PCR to analyse the gene expression of circadian clock genes and the downstream DNA repair gene OGG1 in keratinocytes irradiated with UV-B. In vivo study to determine skin parameters dependent on the circadian cycle and interference of cosmetic formulations to them by assessment of morning and evening values at each measurement day after 28, 56 and 84 days of the study. RESULTS: UV-B irradiation leads to a pronounced delay in circadian clock and downstream gene expression which interferes in the proper function of epidermal stem cells and as thus skin function. The use of a cosmetic active ingredient prevents cyclobutane pyrimidine dimer formation, protects epidermal stem cells and resets the circadian gene expression. It preserves the circadian changes in skin hydration, reduces daily fluctuations of skin redness and strengthens the skin barrier. CONCLUSION: The skin has its own circadian biorhythm to gain full functionality. Interruption of this oscillation will lead to functional impairments. Here we show a cosmetic solution to protect and preserve the skin's circadian rhythm. DNA protection, ROS elimination and stimulation of circadian gene expression seem to be crucial to keep the skin in balance.

OBJECTIF: Le rythme circadien a été mis en lumière par l'attribution du prix Nobel de physiologie/médecine à Jeffrey Hall, Michael Rosbash et Michael Young fin 2017. De nombreuses publications ont élucidé les mécanismes moléculaires qui régissent les biorythmes circadiens de notre corps, des organes périphériques et de chaque cellule. Cependant, il existe peu de connaissances sur le rythme circadien de la peau, qui possède sa propre horloge circadienne périphérique, avec les formules cosmétiques. L'horloge épidermique de la peau est excessivement influencée par des facteurs environnementaux comme les rayons UV ou le mode de vie moderne, qui peuvent induire un "décalage horaire de l'épiderme". Nous donnons ici un aperçu des connaissances actuelles sur l'horloge circadienne épidermique et proposons une solution cosmétique pour protéger et préserver le biorythme de la peau. MÉTHODES: Test RT-PCR quantitatif pour analyser l'expression des gènes de l'horloge circadienne et du gène de réparation de l'ADN OGG1 en aval dans des kératinocytes irradiés aux UV-B. Étude in vivo pour determiner les paramètres cutanés dépendant du cycle circadien et l'interférence des formules cosmétiques sur ces paramètres par évaluation des résultats du matin et du soir à chaque jour de mesure après à 28, 56 et 84 jours d'étude. RÉSULTATS: L'irradiation aux UV-B entraîne un retard prononcé de l'horloge circadienne et de l'expression des gènes en aval, ce qui interfère avec le bon fonctionnement des cellules souches épidermiques et donc en conséquence avec la fonction de la peau. L'utilisation d'un principe actif cosmétique empêche la formation de dimère de cyclobutane pyrimidine, protège les cellules souches épidermiques et rétablit l'expression génique circadienne. Il préserve les changements circadiens dans l'hydratation de la peau, réduit les fluctuations quotidiennes des rougeurs cutanées et renforce la barrière cutanée. CONCLUSION: La peau a son propre biorythme circadien pour acquérir une assurer une parfaite fonctionnalité. L'interruption de cette oscillation entraînera des troubles fonctionnels. Nous présentons ici une solution cosmétique pour protéger et préserver le rythme circadien de la peau. La protection de l'ADN, l'élimination des ROS et la stimulation de l'expression des gènes circadiens semblent être cruciales pour maintenir l'équilibre de la peau.

Grifolin derivatives from Albatrellus ovinus as TRPV1 receptor blockers for cosmetic applications.

OBJECTIVE: Blocking the TRPV1 receptor is an interesting approach for the treatment of sensitive skin. Here we investigated the potential of grifolin derivatives from Albatrellus ovinus to act as TRPV1 receptor blockers and their potential to serve as cosmetic active ingredients. METHODS: Binding characteristics of grifolin derivatives from Albatrellus ovinus were determined in competitive and functional in vitro assays to achieve IC50 values. The TRPV1 receptor was activated in vivo with capsaicin and noxious heat to investigate skin reddening, microcirculation, skin sensations and heat pain thresholds. RESULTS: Grifolin derivatives extracted from Albatrellus ovinus proved to inhibit the TRPV1 receptor in vitro and in vivo. Besides suppression of the TRPV1 receptor activity upon chemical stimulation with capsaicin, thermal activation was shown to be inhibited as well by application of cosmetic formulations containing 3% Albatrellus ovinus extract. The reduction of stinging and burning sensations as well as reduction of reddening and microcirculation upon irritation with capsaicin or thermal stress proved efficacy in vivo. CONCLUSION: Grifolin derivatives from Albatrellus ovinus are able to serve as fungal-derived TRPV1 receptor blockers with capability to serve as a cosmetic active ingredient on sensitive skin.

[Congenital vascular malformations (Hauert disease)]. / Angiodysplastische Arthropathie ("Hauert disease").

Patients with congenital vascular malformations often suffer from arthralgia, especially of the lower limbs. This orthopaedic disease pattern is defined as destructive, angiodysplatic arthritis or Hauert disease and leads to very early destruction of the joints. By presenting diagnostic and therapeutic algorithms, Hauert disease is emphasized as a possible differential diagnosis in order to minimize the risk of an incorrect diagnosis which might lead to under-, over-, or even incorrect treatment. A minimally invasive transathroscopic therapy in the early stages can lead to significant improvement of symptoms and prevention of progressive joint destruction.

Stretching dynamics of semiflexible polymers.

We analyze the nonequilibrium dynamics of single inextensible semiflexible biopolymers as stretching forces are applied at the ends. Based on different (contradicting) heuristic arguments, various scaling laws have been proposed for the propagation speed of the backbone tension which is induced in response to stretching. Here, we employ a newly developed unified theory to systematically substantiate, restrict, and extend these approaches. Introducing the practically relevant scenario of a chain equilibrated under some prestretching force f (pre) that is suddenly exposed to a different external force f (ext) at the ends, we give a concise physical explanation of the underlying relaxation processes by means of an intuitive blob picture. We discuss the corresponding intermediate asymptotics, derive results for experimentally relevant observables, and support our conclusions by numerical solutions of the coarse-grained equations of motion for the tension.