关键词: Corneocytes Cosmeceuticals Drug repurposing Melanocytes Melanogenesis Terminal differentiation

来  源:   DOI:10.1016/j.jare.2023.11.013

Abstract:
BACKGROUND: Natural hair curvature and colour are genetically determined human traits, that we intentionally change by applying thermal and chemical treatments to the fibre. Presently, those cosmetic methodologies act externally and their recurrent use is quite detrimental to hair fibre quality and even to our health.
OBJECTIVE: This work represents a disruptive concept to modify natural hair colour and curvature. We aim to model the fibre phenotype as it is actively produced in the follicle through the topical delivery of specific bioactive molecules to the scalp.
METHODS: Transcriptome differences between curly and straight hairs were identified by microarray. In scalp samples, the most variable transcripts were mapped by in situ hybridization. Then, by using appropriate cellular models, we screened a chemical library of 1200 generic drugs, searching for molecules that could lead to changes in either fibre colour or curvature. A pilot-scale, single-centre, investigator-initiated, prospective, blind, bilateral (split-scalp) placebo-controlled clinical study with the intervention of cosmetics was conducted to obtain a proof of concept (RNEC n.92938).
RESULTS: We found 85 genes transcribed significantly different between curly and straight hair, not previously associated with this human trait. Next, we mapped some of the most variable genes to the inner root sheath of follicles, reinforcing the role of this cell layer in fibre shape moulding. From the drug library screening, we selected 3 and 4 hits as modulators of melanin synthesis and gene transcription, respectively, to be further tested in 33 volunteers. The intentional specific hair change occurred: 8 of 14 volunteers exhibited colour changes, and 16 of 19 volunteers presented curvature modifications, by the end of the study.
CONCLUSIONS: The promising results obtained are the first step towards future cosmetics, complementary or alternative to current methodologies, taking hair styling to a new level: changing hair from the inside out.
摘要:
背景:自然的头发曲率和颜色是由遗传决定的人类特征,我们通过对纤维进行热处理和化学处理来有意改变。目前,这些化妆品方法在外部起作用,它们的反复使用对头发纤维质量甚至对我们的健康都是非常有害的。
目的:这项工作代表了一个改变自然头发颜色和曲度的破坏性概念。我们的目标是对纤维表型进行建模,因为它是通过将特定的生物活性分子局部递送到头皮而在卵泡中主动产生的。
方法:通过微阵列鉴定卷发和直发之间的转录组差异。在头皮样本中,通过原位杂交定位了变量最大的转录本.然后,通过使用适当的细胞模型,我们筛选了1200个仿制药的化学库,寻找可能导致纤维颜色或曲率变化的分子。试点规模,单中心,调查员发起的,prospective,盲,我们进行了双边(裂开头皮)安慰剂对照的临床研究,并干预了化妆品,以获得概念证明(RNECn.92938).
结果:我们发现85个基因在卷发和直发之间转录显著不同,以前与这种人类特征无关。接下来,我们将一些变化最大的基因映射到卵泡的内根鞘,加强该细胞层在纤维形状成型中的作用。从药物库筛选中,我们选择了3个和4个命中作为黑色素合成和基因转录的调节剂,分别,在33名志愿者中进一步测试。故意发生特定的头发变化:14名志愿者中有8名表现出颜色变化,19名志愿者中有16名进行了曲率修改,在研究结束时。
结论:获得的有希望的结果是迈向未来化妆品的第一步,对当前方法的补充或替代,将头发造型提升到一个新的水平:从内到外改变头发。
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