Traditional sunscreens have relied on synthetic compounds to protect against harmful ultraviolet (UV) radiation. However, there is increasing interest in utilizing the natural photoprotective properties of microalgae extracts. This approach does not only aim to enhance the stability and efficacy of sun protection formulae but also seeks to reduce the reliance on synthetic sunscreens. This study investigates the encapsulation of Tisochrysis lutea extract (TL) in nanostructured lipid carriers (NLCs) to create a combination (NLC-TL) with enhanced physicochemical stability, antioxidant activity, SPF efficacy, wound healing capacity, and skin hydration. The particle size and ζ-potential were approximately 100 nm and −50 mV, respectively, and both formulations successfully passed the stability tests. The antioxidant activity, measured via DPPH assay, revealed that NLC-TL achieved the highest free radical scavenging activity across all tested concentrations, indicating a synergistic effect. The incorporation of TL in NLCs maintained the sun protection factor (SPF) of a 2% extract solution (1.53 ± 0.13). The wound healing assay indicated that NLC-TLs significantly enhanced wound closure compared to controls and TL alone. Additionally, skin hydration tests on healthy volunteers revealed that NLC-TLs provided superior and sustained hydration effects. These results highlight NLC-TLs’ potential as a multifunctional topical agent for cosmetic and therapeutic applications.

Pleiotrophin (PTN) is a secreted factor that regulates endothelial cell migration through protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) and α_vβ₃ integrin. Genetic deletion of Ptprz1 results in enhanced endothelial cell proliferation and migration, due to the decreased expression of β₃ integrin and the subsequent, enhanced cMet phosphorylation. In the present study, we investigated the effect of PTN and PTPRZ1 on activating the mTORC1 kinase and protein synthesis and identified part of the implicated signaling pathway in endothelial cells. PTN or genetic deletion of Ptprz1 activates protein synthesis in a mTORC1-dependent manner, as shown by the enhanced phosphorylation of the mTORC1-downstream targets ribosomal protein S6 kinase 1 (SK61) and 4E-binding protein 1 (4EBP1) and the upregulation of HIF-1α. The cMet tyrosine kinase inhibitor crizotinib abolishes the stimulatory effects of PTN or PTPRZ1 deletion on mTORC1 activation and protein synthesis, suggesting that mTORC1 activation is downstream of cMet. The mTORC1 inhibitor rapamycin abolishes the stimulatory effect of PTN or PTPRZ1 deletion on endothelial cell migration, suggesting that mTORC1 is involved in the PTN/PTPRZ1-dependent cell migration. The α_vβ₃ integrin blocking antibody LM609 and the peptide PTN_112–136, both known to bind to α_νβ₃ and inhibit PTN-induced endothelial cell migration, increase cMet phosphorylation and activate mTORC1, suggesting that cMet and mTORC1 activation are required but are not sufficient to stimulate cell migration. Overall, our data highlight novel aspects of the signaling pathway downstream of the PTN/PTPRZ1 axis that regulates endothelial cell functions.

Background/Objectives: In the tumor microenvironment, hypoxia regulates genes that support tumor cell invasion and angiogenesis under the control of the hypoxia-inducible transcription factors (HIFs). Pleiotrophin (PTN) is a secreted protein that activates cell migration in endothelial and cancer cells that express α_νβ₃ integrin but has inhibitory effects in cells that do not express α_νβ₃ integrin. In both cases, the protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) seems to mediate the effects of PTN. In the present work, we studied the effect of hypoxia on PTN and PTPRZ1 expression and the functional consequences of this effect. Methods: Western blot, quantitative real-time PCR, and luciferase assays were used to study the impact of hypoxia at the protein, mRNA, and transcriptional levels, respectively. Decoy oligonucleotides (ODNs), siRNA technology, and plasmid overexpression were used to study the involvement of the transcription factors studied. Functional assays were used to study the effect of hypoxia on cell proliferation and migration. Results: Hypoxia increases PTN expression through the transcriptional activation of the corresponding gene in α_νβ₃ integrin-expressing cells. The transcription factors HIF-1α, HIF-2α, and AP-1 mediate the up-regulation of PTN by hypoxia. Functional assays in endothelial cells from PTN knockout mice or endothelial and cancer cells following the downregulation of PTN expression showed that PTN negatively affects chemical hypoxia-induced cell proliferation and migration. In cancer cells that do not express α_νβ₃ integrin, hypoxia or chemical hypoxia inhibits PTN expression in a HIF-1α-, HIF-2α-, and AP-1-independent manner. The expression of PTPRZ1 is up-regulated by chemical hypoxia, is HIF-1α- and HIF-2α-dependent, and seems to limit the activation of HIF-1α, at least in endothelial cells. Conclusions: Hypoxia or chemical hypoxia regulates PTN and PTPRZ1 expressions to restrict the stimulatory effects of hypoxia on endothelial and cancer cell migration.