Dietary supplementation with N-3 polyunsaturated fatty acid-enriched fish oil promotes wound healing after ultraviolet B-induced sunburn in mice.

N-3 polyunsaturated fatty acids (n-3 PUFA) can alleviate ultraviolet B (UVB)-induced skin cancers, but their effects on sunburn and upcoming wound healing remain controversial. This study aimed to explore the impact of n-3 PUFA-enriched fish oil (n-3 PUFA-FO) on UVB-induced sunburns and subsequent healing. Sixty C57BL/6 female mice were divided into two groups. The treated group mice were fed n-3 PUFA-FO for the entire duration of the experiment. Mice in the control group were fed a standard diet. After two weeks of n-3 PUFA-FO feeding, mice were exposed to UVB for 20 min and sacrificed 20 d later. Skin photodamage and lesion area were recorded during wound healing. Epidermal lesion thickness was quantified in hematoxylin and eosin-stained skin sections. Inflammation and macrophage polarization were assessed by qRT-PCR. Oxidative stress and antioxidant enzyme activity were quantified using specific ELISA kits. N-3 PUFA-FO feeding decreased UVB photodamage and accelerated wound healing progression, both of which were coupled with less intense inflammation and increased macrophage M2 phenotype polarization. Furthermore, n-3 PUFA-FO brought about a decrease in malondialdehyde (MDA) levels but increased the activity of catalase (CAT) and glutathione peroxidase (GP), without changing superoxide dismutase (SOD) activity. N-3 PUFA-FO protects against UVB-induced skin photodamage and promotes wound healing by modulating macrophage phenotypic polarization and antioxidant enzyme activities. N-3 PUFA-FO could be a novel therapeutic approach for both the prevention and treatment of sunburns.

Rapamycin and FK506 derivative TH2849 could ameliorate neurodegenerative diseases through autophagy with low immunosuppressive effect.

Autophagy is an essential cellular process concern with cellular homeostasis down-regulated by mTOR, whose activity can be modulated by rapamycin, a kind of lipophilic macrolide antibiotic, through forming a complex with immunophilin FKBP12 essential for mTOR regulation to induce autophagy. Therefore, rapamycin is normally used as a neuron protective agent. The immunophilin FKBP12 binding ligand FK506 is well known as an immunosuppressive agent by inhibiting the calcineurin expression. In this study, we synthesized a series of modified compounds based on the FKBP12 binding moiety to as same as the binding structure of rapamycin and FK506 particularly. We removed the other binding regions of the complex that has the property of immunosuppression. We found that a novel small molecule named TH2849 from these derivative compounds has a significant binding connection with mTOR by comparing to calcineurin. The effects of TH2849 on calcineurin/NFAT were not as significant as FK506, and weak effects on IL2/p34cdc2 /cyclin signaling pathway were also found. Moreover, TH2849 also shows mitochondrial protective effect through stabilizing the mitochondrial structure and transmembrane potential (ΔΨm) and could rescue dopaminergic neurons in MPTP-treated zebrafishes as well as mice models with less immunosuppressive effect. Our present study shows that TH2849 works as a neuroprotective agent possibly by inducing autophagy and low immunosuppressive effect.

Topical Use of Quercetin-Loaded Chitosan Nanoparticles Against Ultraviolet B Radiation.

Ultraviolet radiation is a major risk factor for human skin damage, especially solar ultraviolet-B (UVB) which can induce inflammation, photoaging, and skin cancer. Quercetin (Qu), one of flavonoid family members, has showed protective effects against UVB radiation. However, its application for topical use is limited by low hydrophilicity and poor percutaneous absorption. Herein, we found that Qu, if entrapped into TPP-Chitosan nanoparticles (TCs), can be efficiently uptake by HaCaT cells and easily permeate through the epidermis layer, meanwhile display better stability and low cytotoxicity. We also found that Qu-loaded TCs (QTCs) could notably enhance the effect of Qu on inhibiting the NF-kB/COX-2 signaling pathway as well as ameliorating the skin edema caused by UVB radiation. Therefore, this study provided a method to get rid of Qu's low hydrophilicity, enhance its percutaneous absorption and retention in the skin, and further improve its anti-UVB effect, and demonstrated that Qu-loaded chitosan nanoparticles can be used as the therapeutic agent for topical use against UVB radiation.

Intracellular Fate of Nanoparticles with Polydopamine Surface Engineering and a Novel Strategy for Exocytosis-Inhibiting, Lysosome Impairment-Based Cancer Therapy.

Polydopamine (PDA) coating as a bioinspired strategy for nanoparticles (NPs) has been extensively applied in cancer theranostics. However, a cellular-level understanding of nano-biointeraction of these PDA-coated NPs (PDNPs), which drives the fate of them and acts as a critical step to determine their efficacy, still remains unknown. Herein, we utilized the representative mesoporous silica NPs (MSNs) to be coated with PDA and study their nano-bioactivities in cancer cells. HeLa cell line was utilized as a model in this study. The PDNPs were discovered to be internalized through three specific pathways, that is, Caveolae-, Arf6-dependent endocytosis, and Rab34-mediated macropinocytosis (55%, 20% and 37% of uptake inhibition by nystatin, Arf6 knockdown, and rottlerin, respectively). Autophagy-mediated accumulation of PDNPs in lysosomes was observed and the formed PDA shells shedded in the lysosomes. Almost 40% of the NPs were transported out of cells via Rab8/10- and Rab3/26-mediated exocytosis pathways at our tested level. On the basis of these results, a novel combined cancer treatment strategy was further proposed using drug-loaded MSNs-PDA by (i) utilizing naturally intracellular mechanism-controlled PDA shedding for organelle-targeted release of drugs in lysosomes to generate lysosome impairment and (ii) blocking the demonstrated exocytosis pathways for enhanced therapeutic efficacy.

Protective effects of quercetin on UVB irradiation­induced cytotoxicity through ROS clearance in keratinocyte cells.

Human skin is the body's largest organ that protects against diverse environmental injuries. However, ultraviolet (UV) radiation, which induces a transient increase in the intracellular level of reactive oxygen species (ROS) and leads to a variety of injuries and various skin diseases, has deleterious effects on living organisms. Quercetin is a naturally occurring compound with strong antioxidant action and can successfully scavenge free radicals. In the present study, we investigated the effects and the mechanism of quercetin on UVB­induced cytotoxicity in keratinocyte (HaCaT) cells. The results of this study showed that quercetin (20 µM) significantly blocked UVB irradiation (15 mJ/cm2)­induced intracellular ROS generation. In addition, the ROS clearing ability of quercetin prevented cell membrane and mitochondria from ROS attack and inhibited cell membrane fluidity decrease and mitochondrial membrane depolarization. Moreover, the outflow of cytochrome c and apoptosis were markedly inhibited. These results suggest that the protective effect of quercetin against UVB irradiation­induced toxicity is mainly mediated by the ROS scavenging ability. Thus, quercetin is a potential agent against UVB irradiation­induced skin damage.

The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo.

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. FROM THE CLINICAL EDITOR: Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect.