Effect of L-4-Thiazolylalanine (Protinol™) on skin barrier strength and skin protection.

OBJECTIVES: Skin barrier properties are critical for maintaining epidermal water content, protecting from environmental factors and providing the first line of defense against pathogens. In this study, we investigated the non-proteinogenic amino acid L-4-Thiazolylalanine (L4) as a potential active ingredient in skin protection and barrier strength. METHODS: L4 on wound healing, anti-inflammatory and anti-oxidant properties were evaluated using monolayers and 3D skin equivalents. The transepithelial electrical resistance (TEER) value was used in vitro as a strong indicator of barrier strength and integrity. Clinical L4 efficacy was assessed for the evaluation of the skin barrier integrity and soothing benefits. RESULTS: In vitro treatments of L4 show beneficial effects in wound closure mechanism, and we demonstrate that L4 anti-oxidant benefits with markedly increased HSP70 and decreased reactive oxygen species production induced by UVs exposure. Barrier strength and integrity were significantly improved by L4, confirmed clinically by an increase in 12R-lipoxygenase enzymatic activity in the stratum corneum. In addition, soothing benefits of L4 have been shown clinically with the decrease in redness after methyl nicotinate application on the inner arm and the significant reduction of the erythema and the skin desquamation on the scalp. CONCLUSION: L4 delivered multiple skin benefits by strengthening the skin barrier, accelerating the skin repair process as well as soothing the skin and the scalp with anti-inflammaging effects. The observed efficacy validates L4 as a desirable skincare ingredient for topical treatment.

OBJECTIFS: La barrière cutanée est primordiale pour le maintien d'un épiderme hydraté, sa protection contre les facteurs environnementaux et pour conférer une première ligne de défense contre les pathogènes. Dans cette étude, nous nous intéressons à un aminoacide non-proteinogénique, L-4-Thiazolylalanine (L4) comme potentiel actif cosmétique et évaluons ses effets sur la protection de la peau et le renforcement de la barrière cutanée. MÉTHODES: Les propriétés cicatrisantes, anti-inflammatoires et antioxydantes de L4 ont été déterminées par culture cellulaire et sur modèles de peau 3D. La mesure de la résistance électrique transépithéliale a été utilisée in vitro comme indicateur de la résistance de la barrière de la peau. Des études cliniques ont été réalisées pour évaluer L4 sur ses capacités apaisantes et son impact sur l'intégrité de la barrière cutanée. RÉSULTATS: In vitro, nous déterminons qu'un traitement L4 a des effets bénéfiques dans le processus de cicatrisation mais aussi des propriétés antioxydantes, induisant une augmentation de HSP70 ainsi qu'une diminution de la production d'espèces réactives a l'oxygène induite par rayons UV. Un renforcement de la barrière cutanée et une amélioration de son intégrité sont observés après un traitement L4 et confirme cliniquement par une augmentation de l'activité enzymatique de la 12R-lipoxygenase dans le stratum corneum. De plus, les effets protecteurs de L4 ont été confirmes cliniquement avec une rougeur cutanée diminuée après application de nicotinate de methyle sur l'avant-bras interne ainsi qu'une réduction significative d'érythème et de desquamation cutanée du cuir chevelu. CONCLUSION: L4 offre de multiples bénéfices pour la peau en renforçant la barrière cutanée, accélérant le processus de cicatrisation et offrant des actions anti-inflammatoires apaisantes pour la peau et le cuir chevelu. Cela fait de L4 un ingrédient cosmétique intéressant pour une application topic.

With blood in the joint - what happens next? Could activation of a pro-inflammatory signalling axis leading to iRhom2/TNFα-convertase-dependent release of TNFα contribute to haemophilic arthropathy?

One of the main complications of haemophilia A is haemophilic arthropathy (HA), a debilitating disease with a significant negative impact on motility and quality of life. Despite major advances in the treatment of haemophilia A, many patients still suffer from HA. We wish to develop new treatments for HA, but must first better understand its causes. Our laboratory studies molecular scissors that release the pro-inflammatory cytokine tumour necrosis factor alpha (TNFα) from cells. TNFα is considered the 'fire alarm' of the body - it helps to fight infections, but can also cause diseases such as inflammatory arthritis. We know that the molecular scissors, called TNFα convertase (TACE), and its newly discovered regulator termed iRhom2 can be rapidly activated by small amounts of cytokines, growth factors, and pro-inflammatory mediators present in the blood. We hypothesize that the rapid activation of TACE could help explain one of the unsolved mysteries regarding the development of HA, which is how even small amounts of blood can provoke a persistent inflammatory response. We propose that once blood enters the joint, iRhom2 and TACE are activated to release TNFα and that this could promote the development of HA in a similar manner to that in which it promotes rheumatoid arthritis (RA). We are currently using immune cells stimulated with blood degradation products, and mouse models of HA, to test this hypothesis. If successful, our study could provide the rationale for testing anti-TNF antibodies, which are already used to treat RA, for the treatment of HA. In addition, they might uncover iRhom2 and TACE as attractive new candidate targets for the treatment of HA.

Traditional Amerindian cultivators combine directional and ideotypic selection for sustainable management of cassava genetic diversity.

Plant domestication provides striking examples of rapid evolution. Yet, it involves more complex processes than plain directional selection. Understanding the dynamics of diversity in traditional agroecosystems is both a fundamental goal in evolutionary biology and a practical goal in conservation. We studied how Amerindian cultivators maintain dynamically evolving gene pools in cassava. Farmers purposely maintain diversity in the form of phenotypically distinct, clonally propagated landraces. Landrace gene pools are continuously renewed by incorporating seedlings issued from spontaneous sexual reproduction. This poses two problems: agronomic quality may decrease because some seedlings are inbred, and landrace identity may be progressively lost through the incorporation of unrelated seedlings. Using a large microsatellite dataset, we show that farmers solve these problems by applying two kinds of selection: directional selection against inbred genotypes, and counter-selection of off-type phenotypes, which maintains high intra-landrace relatedness. Thus, cultural elements such as ideotypes (a representation of the ideal phenotype of a landrace) can shape genetic diversity.