MEG3 shuttled by exosomes released from human bone marrow mesenchymal stem cells promotes TP53 stability to regulate MCM5 transcription in keloid fibroblasts.

BACKGROUND: Despite the interest in mesenchymal stem cells (MSC), their potential to treat abnormal scarring, especially keloids, is yet to be described. The present study aimed to investigate the therapeutic potential of exosomes derived from human bone marrow MSCs (hBMSC-Exos) in alleviating keloid formation. METHODS: Exosomes were isolated from hBMSC, and keloid fibroblasts (KFs) were treated with hBMSC-Exos. Cell counting kit-8, wound healing, transwell invasion, immunofluorescence, and western blot assays were conducted to study the malignant phenotype of KFs. Mice were induced with keloids and treated with hBMSC-Exos. The effect of hBMSC-Exos on keloid formation in vivo was evaluated by hematoxylin and eosin staining, Masson staining, immunohistochemistry, and western blotting. The GSE182192 dataset was screened for differentially expressed long non-coding RNA during keloid formation. Next, maternally expressed gene 3 (MEG3) was knocked down in hBMSC to obtain hBMSC-Exossh-MEG3. The molecular mechanism of MEG3 was investigated by bioinformatic screening, and the relationship between MEG3 and TP53 or MCM5 was verified. RESULTS: hBMSC-Exos inhibited the malignant proliferation, migration, and invasion of KFs at same time as promoting their apoptosis, Moreover, hBMSC-Exos reduced the expression of fibrosis- and collagen-related proteins in the cells and the formation of keloids caused by KFs. The reduction in MEG3 enrichment in hBMSC-Exos weakened the inhibitory effect of hBMSC-Exos on KF activity. hBMSC-Exos delivered MEG3 to promote MCM5 transcription by TP53 in KFs. Overexpression of MCM5 in KFs reversed the effects of hBMSC-Exossh-MEG3, leading to reduced KF activity. CONCLUSIONS: hBMSC-Exos delivered MEG3 to promote the protein stability of TP53, thereby activating MCM5 and promoting KF activity.

Exploring the release of hazardous volatile organic compounds from face masks and their potential health risk.

Hazardous chemicals released from the petroleum-derived face mask can be inhaled by wearers and cause adverse health effects. Here, we first used headspace solid-phase microextraction coupled with GC-MS to comprehensively analyze the volatile organic compounds (VOCs) released from 26 types of face masks. The results showed that total concentrations and peak numbers ranged from 3.28 to 197 µg/mask and 81 to 162, respectively, for different types of mask. Also, light exposure could affect the chemical composition of VOCs, particularly increasing the concentrations of aldehydes, ketones, organic acids and esters. Of these detected VOCs, 142 substances were matched to a reported database of chemicals associated with plastic packaging; 30 substances were identified by the International Agency for Research on Cancer (IARC) as potential carcinogenic to humans; 6 substances were classified in the European Union as persistent, bioaccumulative, and toxic, or very persistent, very bioaccumulative substance. Reactive carbonyls were ubiquitous in masks, especially after exposure to light. The potential risk of VOCs released from the face masks were then accessed by assuming the extreme scenario that all the VOC residues were released into the breathing air within 3 h. The result showed that the average total concentration of VOCs (17 µg/m3) was below the criterion for hygienic air, but seven substances, 2-ethylhexan-1-ol, benzene, isophorone, heptanal, naphthalene, benzyl chloride, and 1,2-dichloropropane exceeded the non-cancer health guidelines for lifetime exposure. This finding suggested that specific regulations should be adopted to improve the chemical safety of face masks.