Immunoactivation by Cutaneous Blue Light Irradiation Inhibits Remote Tumor Growth and Metastasis.

An improved innate immunity will respond quickly to pathogens and initiate efficient adaptive immune responses. However, up to now, there have been limited clinical ways for effective and rapid consolidation of innate immunity. Here, we report that cutaneous irradiation with blue light of 450 nm rapidly stimulates the innate immunity through cell endogenous reactive oxygen species (ROS) regulation in a noninvasive way. The iron porphyrin-containing proteins, mitochondrial cytochrome c (Cyt-c), and cytochrome p450 (CYP450) can be mobilized by blue light, which boosts electron transport and ROS production in epidermal and dermal tissues. As a messenger of innate immune activation, the increased level of ROS activates the NF-κB signaling pathway and promotes the secretion of immunomodulatory cytokines in skin. Initiated from skin, a regulatory network composed of cytokines and immune cells is established through the circulation system for innate immune activation. The innate immunity activated by whole-body blue light irradiation inhibits tumor growth and metastasis by increasing the infiltration of antitumor neutrophils and tumor-associated macrophages. Our results elucidate the remote immune modulation mechanism of blue light and provide a clinically applicable way for innate immunity activation.

Blue light promotes vitamin C-mediated ferroptosis of melanoma through specifically upregulating transporter SVCT2 and generating Fe2.

Vitamin C (VC)-based cancer therapy is a promising therapeutic approach for a variety of cancers due to its profound effects on redox reactions and metabolic pathways. However, high administration dosage of VC for necessary therapeutic efficacy for cancers increases the risk of overt side effects and limits its clinical use. Here, we show cutaneous blue light irradiation can specifically upregulate the sodium-dependent vitamin C transporter 2 (SVCT2) of the tumor and increase effectively the VC concentration at the tumor sites by an overall low dosage administration. In the mouse melanoma model, blue light stimulates the SVCT2 expression through the nuclear factor-kappa B (NF-κB) signaling pathway both in vitro and in vivo. The increased cellular VC together with Fe2+ generated by blue light simultaneously elevate cellular oxidative stress and trigger the ferroptosis of melanoma. With this revealed mechanism, the synergistic actions of blue light on the VC transporter and Fe2+ generation lead to a ca. 20-fold reduction in the administration dosage of VC with an effective melanoma elimination and prolonged survival. The work defines the killing mechanism of blue light on VC-based cancer therapy and provides a practical approach for promoting VC uptake. This light-assisted VC therapy is not only highly efficient for melanoma but also considerable for a broad clinical utility.

Identification of mucins and their expression in the vector mosquito Aedes albopictus.

Mucins, the main structural components of vertebrate respiratory, digestive and reproductive tract mucus, as well as insect peritrophic matrix, play important roles in protecting host cells from invading microbes and difficult external environments. Mucins are characterized by highly glycosylated proteins constituting the mucin domain that is rich in repetitive sequences of threonine, serine, and proline (PTS). Despite potential important roles, mosquito mucins remain largely uncharacterized. Here, we performed bioinformatics analyses to identify proteins with PTS repeat domain and predicted 43 mucins or mucin-related proteins in Aedes albopictus. Gene expression analysis revealed that these mucins are dynamically expressed across different development stages and in different organs of Aedes albopictus. Of note, blood feeding upregulated AALF016448 and AALF013291 expression in the midgut, fat body, and ovary, raising the possibility that these mucins play potential roles in reproduction, digestion, and intestinal defense against invading pathogens upon blood feeding. Our in silico identification, followed by expressional validation, thus established a valuable resource for further dissecting the functions of mucins for vector control.