No abstract

No abstract

Human amniotic epithelial cells (hAECs), one of the stem cells identified from the human placenta, possess numerous advantages and have been considered as an attractive and available cell source for regenerative medicine. Accumulating evidence has showed that cellular senescence was one of the pathogenic hubs of diabetic wound chronicity. Keratinocytes and fibroblasts are the primary cells involved in wound healing. Therefore, in this study, we aimed to investigate the antisenescence effects of hAECs on keratinocytes and fibroblasts in diabetic wounds.Sustained hyperglycemia impaired cell function and accelerated senescence in vitro.However, this phenotype was rescued by hAECs-conditioned medium (hAECs-CM), with increased migration and proliferation in keratinocytes and fibroblasts and enhanced collagen synthesis and α-smooth muscle actin (α-SMA) production in fibroblasts. In addition, hAECs-CM dramatically inhibited intracellular reactive oxygen species (ROS) and senescence-associated β-galactosidase (SA-β-gal) in keratinocytes and fibroblasts under high-glucose (HG) condition. Moreover, hAECs-CM could downregulate the increased RAGE and P21 induced by continuous HG stimulation.Intradermal injection of hAECs in diabetic wounds promoted re-epithelialization and granulation tissue formation, accompanied by decreased P21 + cells and increased PCNA + cells in epidermis and dermis, as well as promoted collagen deposition and α-SMA expression. Furthermore, CM-Dil-labeled hAECs survived to Day 5 but disappeared by Day 10 in diabetic wounds. These findings indicated that hAECs could inhibit diabetes-induced premature senescence and enhance the function of keratinocytes and fibroblasts via paracrine effects, partly by inhibiting RAGE/P21 signaling pathway. Thus, hAECs targeting cellular senescence induced by a hyperglycemic environment may be a new strategy for the treatment of diabetic wounds.

Previous work suggests that the experiences of online and offline self‐disclosure are heterogeneous among individuals. Yet little work has been done to identify the moderating role of individual characteristics and pre‐existing relationship characteristics on the diverse relational outcomes. The present study using a 7‐day diary design examined whether individuals' self‐esteem level and relational closeness would moderate the relationships between online and offline self‐disclosure to offline friends and two relational outcomes, that is, relationship satisfaction and trust in friendships. The analyses on 686 diary responses from 98 participants revealed that offline self‐disclosure generally predicted greater relationship satisfaction and trust in friendships, whereas the role of online self‐disclosure was not statistically significant. More importantly, self‐esteem moderated the pattern associated with offline self‐disclosure but not that with online self‐disclosure. Specifically, offline self‐disclosure predicted greater benefits to people with lower self‐esteem relative to people with higher self‐esteem. Moreover, pre‐existing relational closeness moderated the relationship between offline self‐disclosure and trust in friendships such that casual friendships benefited more from offline self‐disclosure than close friendships did. The present study highlights the importance of personal characteristics and relationship characteristics in understanding the heterogeneous relational influence of different communication modes.