Scarless skin regeneration remains a challenge due to the complicated microenvironment involved in wound healing. Here, the hydrophobic drug, asiaticoside (AC), was loaded inside silk nanofiber hydrogels to achieve bioactive and injectable matrices for skin regeneration. AC was dispersed in aqueous silk nanofiber hydrogels with retention of biological functions that regulated inflammatory reactions and vascularization in vitro. After implantation in full-thickness wound defects, these AC-laden hydrogel matrices achieved scarless wound repair. Inflammatory reactions and angiogenesis were regulated during inflammation and remodeling, which was responsible for wound regeneration similar to normal skin. Both in vitro and in vivo studies demonstrated promising applications of these AC-laden silk hydrogels towards scarless tissue regeneration.

Circular RNAs (circRNAs) are emerging regulators in the development of human cancers. However, the role of circRNAs in melanoma is poorly understood. Microarray analysis and qRT-PCR was applied to screen out circRNAs that were differentially expressed in melanoma cells compared to normal cells. Currently, we first proved that inhibition of CYR61, an angiogenesis factor with controversial functions in melanoma, restrained cell migration, invasion and angiogenesis in melanoma. Thereafter, a novel circRNA hsa_circ_0027247 derived from GLI1 (circ-GLI1) was identified to positively modulate CYR61 expression in melanoma cell lines. Besides, silencing circ-GLI1 hindered melanoma cell metastasis as well. Interestingly, we unveiled that circ-GLI1 enhanced CYR61 transcription by an indirect manner. Meanwhile, circ-GLI1 activated Hedgehog/GLI1 and Wnt/β-catenin pathways by affecting the degradation of GLI1 and β-catenin. Moreover, we found that circ-GLI1 interacted with p70S6K2 to induce GSK3β phosphorylation at Ser9, and therefore blocked the binding of GSK3β with GLI1 and β-catenin so as to elevate their protein expression. Of note, CYR61 was transcriptionally activated by MYC, a well-recognized downstream target of both GLI1 and β-catenin. In conclusion, circ-GLI1 exacerbates the metastasis and angiogenesis of melanoma by upregulating Cyr61 via p70S6K2-dependent activation of Hedgehog/GLI1 and Wnt/β-catenin pathways.

Background: To date, no studies compared curative effects of thermal lesions in deep and superficial dermal layers in the same patient (face-split study). Objective: To evaluate skin laxity effects of microneedle fractional radiofrequency induced thermal lesions in different dermal layers. Methods and Materials: 13 patients underwent three sessions of a randomized face-split microneedle fractional radiofrequency system (MFRS) treatment of deep dermal and superficial dermal layer. Skin laxity changes were evaluated objectively (digital images, 2 independent experts) and subjectively (patients’ satisfaction numerical rating). Results: 12 of 13 subjects completed a course of 3 treatments and a 1-year follow-up. Improvement of nasolabial folds in deep dermal approach was significantly better than that in superficial approach at three months (P=.0002) and 12 months (P=.0057) follow-up. Effects on infraorbital rhytides were only slightly better (P=.3531). Conclusion: MFRS is an effective method to improve skin laxity. Thermal lesion approach seems to provide better outcomes when applied to deep dermal layers. It is necessary to consider the skin thickness of different facial regions when choosing the treatment depth.

The treatment of hypertrophic scar (HS) has thus far been a clinical challenge. We evaluated the therapeutic effect of CO ₂ fractional laser combined with 5-fluorouracil ethosomal gel (5-FU EG) in rabbit HS model. HS model was established as standardized scars on the ventral surface of rabbit ears, divided into four groups: control (no intervention), EG treatment, laser treatment, and combined treatment group (laser plus 5-FU EG). Clinical macroscopic and H&E-stained microscopic observations were conducted to assess HS improvement. The mRNA levels of types I and III collagen, transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6) were detected by real-time PCR. After 14 days, H&E staining shows that the thickness of HS in treatment groups was significantly lower compared with the control group, and the thickness in laser treatment group and combined treatment group was significantly lower compared with the EG treatment group. The mRNA levels of types I and III collagen, TGF-β1 were significantly low in all treatment groups, whereas IL-6 was highest in the laser treatment group at day 14. The macro- and microscopic effects of the combined and CO ₂ fractional laser treatment were better compared with 5-FU EG only. Inhibition of types I and III collagen, TGF-β1 are the possible underlying mechanism of action, whereas the function of IL-6 remains to be further studied. Our study suggests that the effect of combined 5-FU EG and laser, as well as laser-only treatment are superior to 5-FU EG monotreatment. The mechanism of HS improvement is related to reduction of collagen I/III and the inhibition of TGF-β1 expression.