BACKGROUND: Visible light, in particular blue light, has been identified as an additional contributor to cutaneous photoageing. However, clinical studies demonstrating the clear effect of blue light on photoageing are still scarce, and so far, most studies have focused on broad-spectrum visible light. Although there is evidence for increased skin pigmentation, the underlying mechanisms of photoageing in vivo are still unclear. Furthermore, there is still a need for active ingredients to significantly protect against blue light-induced hyperpigmentation in vivo. Our study had two aims: to detect visible changes in skin pigmentation following repeated irradiation of the skin with LED-based blue light and to reduce pigmentation using suitable active ingredients. METHOD: We conducted a randomized, double-blind and placebocontrolled clinical study on 33 female volunteers with skin phototypes III and IV. We used a repetitive blue light (4 9 60 J cm À2 , 450 nm) irradiation protocol on the volunteers' inner forearms. Using hyperspectral imaging, we assessed chromophore status. In addition, we took chromameter measurements and photographs to assess visible hyperpigmentation. RESULTS: We measured significant changes in chromophore status (P < 0.001 vs baseline), that is of melanin, haemoglobin and oxygen saturation, immediately after blue light irradiation. In addition, we found visible skin colour changes which were expressed by a significant decrease in ITA°values (delta ITA°= À16.89, P < 0.001 vs baseline for the placebo group) and an increase in a* (delta a* = +3.37, P < 0.001 vs baseline for the placebo group) 24 h post-irradiation. Hyperpigmentation and skin reddening were mitigated by both a formulation containing 3% of a microalgal product and a formulation containing 3% niacinamide. CONCLUSION: Our study sets out an efficient and robust protocol for investigating both blue light-induced cutaneous alterations, such as changes in skin chromophores, and signs of photoageing, such as hyperpigmentation. Moreover, we have shown evidence that both an extract of the microalga Scenedesmus rubescens and niacinamide (vitamin B3) have the potential to protect against blue light-induced hyperpigmentation.

One of the first lines of cutaneous defense against photoaging is (a) the synthesis of melanin and (b) the initiation of an oxidative stress response to protect skin against the harmful effects of solar radiation. Safe and selective means to stimulate epidermal pigmentation associated with oxidative stress defense are; however, scarce. Activation of the melanocortin-1 receptor (MC1R) on epidermal melanocytes represents a key step in cutaneous pigmentation initiation and, additionally, it regulates cellular defense mechanisms like oxidative stress and DNA-repair. Thus, making the activation of MC1R an attractive strategy for modulating skin pigmentation and oxidative stress. In this context, we designed and synthesized pentapeptides that act as MC1R agonists. These peptides bound, with high potency, to MC1R and activated cAMP synthesis in CHO cells expressing human MC1R. Using one lead pentapeptide, we could show that this activation of MC1R was specific as testing the activation of other G-protein coupled receptors, including the MC-receptor family, was negative. In vitro efficacy on mouse melanoma cells showed similar potency as for the synthetic MC1R agonist alpha-melanocyte stimulating hormone (NDP-alpha-MSH). Moreover, we could reproduce this activity in human skin tissue culture. The lead pentapeptide was able to induce ex-vivo protein expression of key melanogenesis markers melanocyte inducing transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP-1). Concerning oxidative stress response, we found that the pentapeptide enhanced the activation of Nrf2 after UVA-irradiation. Our results make this pentapeptide an ideal candidate as a skin pigmentation enhancer that mimics alpha-MSH and may also have anti-photoaging effects on the skin.

An extract of Scenedesmus rubescens showed broad activity against markers of UV irradiation-induced cutaneous ageing. It may therefore be used as a preventive or regenerative agent for anti-ageing strategies.

Purpose There is no evidence-based definition of early recurrence following resection of colorectal cancer. The purpose of this study is to define a point that discriminates between early and late recurrence in patients who have undergone colorectal cancer resection with curative intent and to analyze associated risk factors. Methods A retrospective single-center cohort study was performed at a university hospital recognized as a comprehensive cancer center, specializing in colorectal cancer surgery. Patient data were retrieved from a prospectively maintained institutional database. Included patients underwent resection for primary, non-metastatic colorectal carcinomas with curative intent between 1995 and 2010. Aims of the study were (1) to define the optimal cut-off point of recurrence-free survival based on overall survival using a minimum p value approach and (2) to identify patterns of initial recurrence and putative risk factors for early recurrence using regression models. Results Recurrence was diagnosed in 412 of 1893 patients. Statistical analysis suggested that a recurrence-free survival of 16 months could be used to distinguish between early and late recurrence based on overall survival (p < 0.001). Independent risk factors for early recurrence included advanced pT categories (pT3,4/ypT3,4) and positive lymph node status (pN+/ypN+). Early recurrence was independent of site of recurrence and was associated with worse prognosis. Conclusions Recurrence of colorectal carcinoma within 16 months after primary treatment should be labeled as “early.” Tumor categories pT3,4/ypT3,4 and positive lymph node status pN+/ypN+ are predictive of early recurrence.

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