NANOG is a key transcription factor required for maintaining pluripotency of embryonic stem cells. Elevated NANOG expression levels have been reported in many types of human cancers, including lung, oral, prostate, stomach, breast, and brain. Several studies reported the correlation between NANOG expression and tumor metastasis, revealing itself as a powerful biomarker of poor prognosis. However, how NANOG regulates tumor progression is still not known. We previously showed in medaka fish that Nanog regulates primordial germ cell migration through Cxcr4b, a chemokine receptor known for its ability to promote migration and metastasis in human cancers. Therefore, we investigated the role of human NANOG in CXCR4-mediated cancer cell migration. Of note, we found that NANOG regulatory elements in the CXCR4 promoter are functionally conserved in medaka fish and humans, suggesting an evolutionary conserved regulatory axis. Moreover, CXCR4 expression requires NANOG in human glioblastoma cells. In addition, transwell assays demonstrated that NANOG regulates cancer cell migration through the SDF1/CXCR4 pathway. Altogether, our results uncover NANOG-CXCR4 as a novel pathway controlling cellular migration and support Nanog as a potential therapeutic target in the treatment of Nanog-dependent tumor progression.

A novel amino-nanozyme, based on boehmite nanoparticles (BNPs) functionalised with a tetra-azapyridinophane (L1), has been designed to undermine some of the key issues underlying Huntington disease. L1 forms Cu2+ complexes...

Continuous overexposure to sunlight increases its harmful effects on the skin. For this reason, there is a growing need to characterize economic models more representative of the negative effects and counteracting responses that irradiation causes on human skin. These models will serve for the screening of protective compounds against damage caused by ultraviolet (UV) and high energy visible light (HEV). Therefore, two common in vitro models employed for sunlight irradiation studies, namely human keratinocyte HaCat culture and reconstructed human epidermis (RHE), were compared with the medaka fish embryo model, traditionally used in other scientific disciplines. Using suberythemal doses of UVA and HEV to determine the level of Reactive Oxygen Species (ROS) generation and thymine dimers formed by UVB, we show that medaka embryo responds with a lower damage level, more comparable to human skin, than the other two models, probably due to the protective mechanisms that work in a complete organism. In the same way, the protective effects of antioxidant compounds have the greatest effect on medaka embryos. Taken together, these findings suggest that medaka embryos would be a good alternative in vitro model for sunlight effect studies, and for the screening of molecules with counteracting capacity against the damage caused by UV and HEV.

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder, of the so-called minority diseases, due to its low prevalence. It is caused by an abnormally long track of glutamines (polyQs) in mutant huntingtin (mHtt), which makes the protein toxic and prone to aggregation. Many pathways of clearance of badly-folded proteins are disrupted in neurons of patients with HD. In this work, we show that one Mn(II) quinone complex (4QMn), designed to work as an artificial superoxide dismutase, is able to activate both the ubiquitin-proteasome system and the autophagy pathway in vitro and in vivo models of HD. Activation of these pathways degrades mHtt and other protein-containing polyQs, which restores proteostasis in these models. Hence, we propose 4QMn as a potential drug to develop a therapy to treat HD.

In the present study, selected cosmeceutical properties of aqueous extracts from the microalgae strain Trachydiscus minutus were assessed and compared with those obtained using three widely used Chlorella strains (C. vulgaris, C. sorokiniana, and C. minutissima). Among all extracts, T. minutus extracts showed the highest total antioxidant capacity (TAC) and inhibitory potency towards elastase, suggesting potential activity in controlling skin aging. Furthermore, the cytotoxicity, anti-inflammatory activity and UVA protection of T. minutus extract were evaluated employing normal human dermal fibroblasts (NHDF) and human keratinocyte HaCaT cells. The results showed that the T. minutus extract was able to significantly inhibit the transcription of selected marker genes involved in inflammation [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα)]. In addition, treatment of NHDF and HaCaT cells with T. minutus extract ameliorate the UVA-induced cell damage by decreasing the accumulation of reactive oxygen species (ROS). Extracts from T. minutus were formulated into a skin care cream and an aqueous gel. Both formulas exhibited excellent compatibility and stability. Comprehensively, all these results suggest that T. minutus extract displays promising cosmeceutical properties by providing antioxidant, anti-aging, and anti-inflammatory activities, and therefore has potential for cosmeceutical use.