Exosomes From ADSCs Attenuate Bleomycin-Induced Skin Fibrosis And Oxidative Stress In Scleroderma Via Circ-Zfyve9 Delivery

Background: Systemic sclerosis (SSc) is autoimmune trait affecting several organs, which is identified by thickening of dermis and connective tissue affected by collagen accumulation, as well as vascular injuries inducing hypoxia. Methods: In this investigation, adipose-derived stem cells (ADSCs) were separated from the ADSC exosomes and a bleomycin-induced SSc mouse model was constructed. We employed high-throughput sequencing to study abnormal expression of circular RNAs (circRNAs) in SSc skin tissues with or without ADSC exosome treatment. The regulatory mechanism and targets were studied using bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation experiments, and RT-qPCR detection. Results: ADSC exosome treatment prevented dermal thickening and fibrosis in bleomycin-induced scleroderma. In addition, circ-Zfyve9 was demonstrated to have an important function in ADSC exosome-mediated skin tissue protection. GPX4 and miR-135 were shown to be circ-Zfyve9 downstream targets. Overexpressing miR-135 or downregulating GPX4 reversed circ-Zfyve9 promotion effects rupon angiopoiesis by promoting lipidosome ROS in EPCs under hypoxic conditions. Overexpressing miR-135 or downregulating GPX4 reversed the circ-Zfyve9 inhibition effect on fibrosis in myofibroblasts under hypoxic conditions. Overexpressing circ-Zfyve9 increased the therapeutic effect of ADSC exosomes. Conclusions: Taken together, the present study results show that the exosomes from ADSCs attenuate bleomycin-induced skin fibrosis and oxidative stress in scleroderma via circ-Zfyve9 delivery.

Microneedle Radiofrequency Combined with Human Fibroblast Conditioned Media for Acne Scars and Skin Rejuvenation

Background: Acne vulgaris is one of the most common dermatology problems in the world. Acne scar can cause stress for sufferers. Microneedle Radiofrequency (MR) clinically has an effectiveness treating acne, acne scars and skin aging. MR acting as electrodes and directly deliver radiofrequency energy deep into the skin to induce new collagen production, dermal thickening and re epitelization. Cases: Seventeen patients (12 acne scar and 5 aging patients, 25-50 years old, Fitzpatrick skin type III-IV) with acne scars and aging skin who received three sessions of microneedle radiofrequency treatment for 2 months at 3 weeks intervalper session. Discussion: We use Goodman and Baron’s Global Acne Scarring System to assess the improvement of acne scars. It showed that by qualitative grading system from 12 patients (grade 3 and grade 4 acne scars), 58% patients showed 2 grade improvement, 33% showed1 grade improvement and 8.3% showed 3 grade improvement. Quantitative assessment showed that 58,3% of the patients had moderate improvement, 25% had good improvement and 16,6% had very good improvement. Global Aesthetic Improvement Scale (GAIS) are used to assess the improvement in skin texture, wrinkles graded by physician. It showed 60 % patients has 51 to 75% improvement and 40% patients has 26 to 50% improvement.

Changes in skin thickness and elasticity

This chapter deals with many skin conditions that alter the texture and properties of the skin. When assessing the skin, it is important to look and feel for signs of abnormal texture (thickening, atrophy, and changes in extensibility and elasticity). This will help determine the site and depth of pathology within the skin. Textural changes of the skin arise due to alterations in the epidermis, dermis, and/or subcutaneous fat. In some conditions, dependant on the stage of the disease there may be a mixture of the above (e.g. epidermal thinning occurs in morphoea but also a dermal thickening so that the skin feels thickened and firm on palpation). Similarly, in dermatomyositis there is localized dermal thickening in the form of calcinosis but eventual atrophy of the fat layer may occur (lipoatrophy).

Inactivation of evenness interrupted (EVI) reduces experimental fibrosis by combined inhibition of canonical and non-canonical Wnt signalling

ObjectivesCanonical as well as non-canonical Wnt signalling pathways have emerged as core pathways of fibrosis. Their profibrotic effects are mediated via distinct intracellular cascades independently of each other. Thus, inhibition of both pathways may have additive antifibrotic effects. Here, we knocked down evenness interrupted (EVI) to simultaneously target for the first time canonical and non-canonical Wnt signalling in experimental fibrosis.MethodsThe antifibrotic effects of siRNA-mediated knockdown of EVI were evaluated in the mouse models of bleomycin-induced skin fibrosis and in fibrosis induced by adenoviral overexpression of a constitutively active TGF-β receptor I (AdTBRI).ResultsKnockdown of EVI decreased the release of canonical and non-canonical Wnt ligands by fibroblasts and reduced the activation of canonical and non-canonical Wnt cascades in experimental fibrosis with decreased accumulation of β-catenin and phosphorylated JNK and cJun. Inactivation of EVI exerted potent antifibrotic effects and reduced dermal thickening, myofibroblast differentiation and accumulation of collagen in the mouse models of bleomycin-induced and AdTBR-induced fibrosis.ConclusionsInhibition of Wnt secretion by knockdown of EVI inhibits canonical and non-canonical Wnt signalling and effectively reduces experimental fibrosis in different preclinical models. Inhibition of Wnt secretion may thus be an interesting approach for the treatment of fibrosis.