Department of Biomedical Science, Faculty of Health and Society, Malmö University, 205 06, Malmö, Sweden.
Biofilms-Research Center for Biointerfaces, Malmö University, 205 06, Malmö, Sweden.
Sci Rep. 2021 Jan 12;11(1):678. doi: 10.1038/s41598-020-79903-w.
The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.
色氨酸到犬尿氨酸的比值（Trp/Kyn）已被提议作为癌症生物标志物。因此，非侵入性的局部取样 Trp/Kyn 可以作为皮肤癌诊断的有前途的概念。通过进行体外猪皮渗透研究，我们得出结论，非侵入性的局部取样 Trp 和 Kyn 是可行的。我们探讨了不同实验条件的影响，这些条件与临床体内环境相关，例如 pH 值变化、取样时间和 Trp 和 Kyn 的微生物降解。Trp 和 Kyn 的渗透性总体上相似。然而，由于内源性 Trp，渗透的 Trp/Kyn 比值通常高于 1，应考虑在内，以获得准确反映系统浓度的非偏倚 Trp/Kyn 比值。此外，延长取样时间与细菌 Trp 和 Kyn 降解有关，在临床环境中应加以考虑。最后，实验结果得到了四个渗透途径模型的支持，该模型预测亲水性 Trp 和 Kyn 分子主要通过脂质缺陷（即多孔途径）渗透。然而，Trp 的疏水性吲哚环被认为导致 Trp 通过 SC 脂质层的扩散有一个小但明显的相对增加，而旁路途径被提议略微有利于 Kyn 相对于 Trp 的渗透。
