Electric fields reverse the differentiation of keratinocyte monolayer by down-regulating E-cadherin through PI3K/AKT/Snail pathway.

Re-epithelialization is an important step in skin wound healing, referring to the migration, proliferation, and differentiation of keratinocytes around the wound. During this process, the edges of the wound begin to form new epithelial cells, which migrate from the periphery of the wound towards the center, gradually covering the entire wound area. These newly formed epithelial cells proliferate and differentiate, ultimately forming a protective layer over the exposed dermal surface. Wound endogenous electric fields (EFs) are known as the dominant factor to facilitate the epidermal migration to wound center. However, the precise mechanisms by which EFs promote epidermal migration remains elusive. Here, we found that in a model of cultured keratinocyte monolayer in vitro, EFs application reversed the differentiation of cells, as indicated by the reduction of the early differentiation markers K1 and K10. Genetic manipulation confirmed that EFs reversed keratinocyte differentiation through down-regulating the E-cadherin-mediated adhesion. By RNA-sequencing analysis, we screened out Snail as the transcription suppressor of E-cadherin. Snail knockdown abolished the down-regulation of E-cadherin and the reversal of differentiation induced by EFs. KEGG analysis identified PI3K/AKT signaling for Snail induction under EFs. Inhibition of PI3K by LY294002 diminished the EFs-induced AKT activation and Snail augmentation, largely restoring the level of E-cadherin reduced by EFs. Finally, in model of full-thickness skin wounds in pigs, we found that weakening of the wound endogenous EFs by the direction-reversed exogenous EFs resulted in an up-regulation of E-cadherin and earlier differentiation in newly formed epidermis in vivo. Our research suggests that electric fields (EFs) decrease E-cadherin expression by suppressing the PI3K/AKT/Snail pathway, thereby reversing the differentiation of keratinocytes. This discovery provides us with new insights into the role of electric fields in wound healing. EFs intervene in intracellular signaling pathways, inhibiting the expression of E-cadherin, which results in a lower differentiation state of keratinocytes. In this state, keratinocytes exhibit increased migratory capacity, facilitating the migration of epidermal cells and wound reepithelialization.

Ultra-Hydrophobic Gauze Driving Super-Haemostasis.

Controlling bleeding by applying pressing cotton gauze is the most facile treatment in prehospital emergencies. However, the wettable nature of cotton fibers leads to unnecessary blood loss due to excessive blood absorption, inseparable adhesion-induced pain, and pliable to infection. Here, a kind of ultra-hydrophobic haemostatic anti-adhesive gauze whose surface is loaded with polydimethylsiloxane (PDMS) and hydrophobic-modified cellulose nanocrystals (CNCs), achieving a water contact angle of ≈160° is developed. It is demonstrated that the mechanism by which hydrophobic CNCs promote blood clotting is associated with their ability to activate coagulation factors, contributing to fibrin formation, and promoting platelet activation. The blood-restricting effect results from the low surface energy layer formed by PDMS and then the alkyl chains of hydrophobic CNCs are combined. The produced ultra-hydrophobic gauze resists blood flow and diffusion, decreases blood loss, is effortlessly peelable, and minimizes pathogen adhesion. Compared to the commercial cotton gauze, this gauze achieved effective haemostasis and antiadhesion by reducing blood loss by more than 90%, shortening haemostasis time by more than 75%, lowering peeling force by more than 90% and minifying bacterium attachment by more than 95%. This work presents promising applications in terms of prehospital first aid.

A Network Meta-analysis to Explore the Effectiveness of the Different Treatment Modalities in Acne Scars.

BACKGROUND: Multiple treatments are used to treat acne scars, but comparing the effectiveness of these treatments have not been studied yet. This research aimed to conduct a complete analysis of the effectiveness of commonly used therapies in acne scars. METHODS: PubMed, Embase, and Cochrane's Library (Cochrane Center Register of Controlled Trials) databases were searched through May 2023. We used patient satisfaction score as the primary outcome and Goodman Baron qualitative scar grading system as the secondary outcome to evaluate the effectiveness of different commonly used therapies for acne scarring, including laser, microneedling (MN), platelet-rich plasma (PRP), autologous fat grafting and combined therapies. RESULTS: Herein, 495 patients from 13 studies were included. Our results showed that PRP combined with laser was the most effective among therapies in treating acne scars. Ranking of effectiveness by the surface under the cumulative ranking (SUCRA) curve for patient satisfaction score was as following: PRP + laser (96.2%) > laser (71.2%) > MN (45.5%) > MN + PRP (42.0%) > autologous fat grafting (24.5%) > PRP (20.5%). Additionally, ranking of effectiveness by the SUCRA curve for Goodman Baron qualitative scar grading system was as following: PRP + laser (86.3%) > laser (64.2%) > MN + PRP (54.2%) > MN (37.2%) > PRP (8.1%). CONCLUSION: This network meta-analysis indicated that the combined therapy of PRP and laser might be the most effective. Additionally, more high-quality randomized controlled trials are needed to verify our findings. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .