First‐ and third‐generation retinoids are the main treatment for acne. Even though efficacious, they lack full selectivity for retinoic acid receptor (RAR) γ, expressed in the epidermis and infundibulum.

First- and third-generation retinoids even though efficacious in acne, lack full selectivity for RARγ expressed in the epidermis and infundibulum. We describe the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. Trifarotene is a selective RARγ agonist with >20-fold selectivity over RARa and RARβ. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0.01% applied topically is highly comedolytic and has antiinflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, RA metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after four weeks of topical application of trifarotene 0.005% cream. Based on its RARg selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene could result in good efficacy and may present a favorable safety profile in acne and ichthyotic disorders.

Acne is a chronic inflammatory skin disease, linked to changes in hormone levels. It mainly affects adolescents and young adults, and may lead to permanent scarring. 1.5 billion people aged between 15 and 45 suffer from some form of acne – mild, moderate or severe. Retinoic acid is one type of treatment for acne, and there are several different types, which are applied directly to the skin (topically). Trifarotene is a new type of retinoic acid which is able to act against only one particular retinoic acid receptor, and this study looked at whether it might be suitable for use in acne and other skin diseases, and potentially have an improved efficacy and safety profile compared with less selective retinoids (i.e. ones that target more than one retinoic acid receptor). Looking at the biological pathways of the drug, the authors suggest that it should be very effective in acne. Furthermore, trifarotene is expected to be rapidly eliminated in the blood stream, thereby potentially leading to fewer side effects and making it particularly useful for the treatment of large skin surface areas, such as the back and chest of acne patients. Based on these favourable characteristics of trifarotene, it is worth now investigating the clinical efficacy of this retinoid.

痤疮是一种慢性炎症性皮肤病,与激素水平变动有关。它主要影响青少年和年轻人,可能导致永久性疤痕。15亿15岁至45岁之间的人群曾患上某种形式的痤疮 ‐ 轻度、中度或重度。视黄酸是痤疮的一类治疗方法,存在多种不同类型,可直接敷用在皮肤上(局部)。Trifarotene是新型视黄酸,能够只针对一种特定的视黄酸受体起作用,而本研究调查了它是否适用于痤疮和其他皮肤疾病,并且与选择性更低的视黄酸(即针对多个视黄酸受体)相比是否可能改善疗效和安全性。通过调查药物的生物学途径,作者表示,该药物应该对痤疮非常有效。此外,trifarotene将在血流中迅速消失,因此可能会减少副作用,使其特别适用于治疗大面积的皮肤表面部位,比如痤疮患者的背部和颈部。基于trifarotene的这些有利特征,此视黄酸的临床效果目前很值得研究。

BACKGROUND:Clobetasol propionate shampoo is effective and safe in treatment of scalp psoriasis (SP). Gene expression profiling of psoriatic skin biopsies led to the identification of numerous disease-related genes. However, it remained unknown whether the gene expression profile of hair follicles of SP patients was also affected.OBJECTIVES:To determine whether psoriasis-related genes are differentially regulated in the hair follicles of SP patients and whether the modulation of these genes can be correlated with clinical severity scores.METHODS:A single arm, open study was conducted in three centres. SP patients received daily treatment with clobetasol propionate shampoo. At Baseline, Weeks 2 and 4, investigators assessed clinical severity parameters and collected scalp hair follicles in anagen phase. Total RNA extracted from hair follicles was used to determine the expression level of 44 genes, which were reported previously to be upregulated in the skin of psoriasis patients.RESULTS:RNA of good quality and sufficient quantity was obtained from hair follicles of psoriasis patients and healthy volunteers (HV). The expression level of 10 inflammation-related genes was significantly increased in psoriatic hair follicles. The patient's exploratory transcriptomic score, defined as the mean fold modulation of these 10 genes compared with HV, correlated with clinical severity scores. Clobetasol propionate shampoo was effective in decreasing both the exploratory transcriptomics and the clinical severity scores.CONCLUSION:Hair follicles of SP patients are affected by the inflammatory process. The change in the expression level of inflammation-related genes correlates with the severity of the disease.

MOTIVATIONMicroarray technology has become a powerful research tool in many fields of study; however, the cost of microarrays often results in the use of a low number of replicates (k). Under circumstances where k is low, it becomes difficult to perform standard statistical tests to extract the most biologically significant experimental results. Other more advanced statistical tests have been developed; however, their use and interpretation often remain difficult to implement in routine biological research. The present work outlines a method that achieves sufficient statistical power for selecting differentially expressed genes under conditions of low k, while remaining as an intuitive and computationally efficient procedure.RESULTSThe present study describes a Global Error Assessment (GEA) methodology to select differentially expressed genes in microarray datasets, and was developed using an in vitro experiment that compared control and interferon-gamma treated skin cells. In this experiment, up to nine replicates were used to confidently estimate error, thereby enabling methods of different statistical power to be compared. Gene expression results of a similar absolute expression are binned, so as to enable a highly accurate local estimate of the mean squared error within conditions. The model then relates variability of gene expression in each bin to absolute expression levels and uses this in a test derived from the classical ANOVA. The GEA selection method is compared with both the classical and permutational ANOVA tests, and demonstrates an increased stability, robustness and confidence in gene selection. A subset of the selected genes were validated by real-time reverse transcription-polymerase chain reaction (RT-PCR). All these results suggest that GEA methodology is (i) suitable for selection of differentially expressed genes in microarray data, (ii) intuitive and computationally efficient and (iii) especially advantageous under conditions of low k.AVAILABILITYThe GEA code for R software is freely available upon request to authors.