Zhe Jian

Autologous epidermal cell suspension (AECS) transplantation is essential for treating large-area depigmenting diseases and some chronic wounds that are refractory to conservative therapy. However, this technique encounters challenges, including limited repigmentation efficacy and high costs, which have hindered its clinical adoption. To enhance the repigmentation efficacy of AECS, our research explored the optimal conditions for preparing suspensions of epidermal cells (ECs). Next, we investigated the functions of melanocytes (MCs) and repigmentation efficacy through co-culturing and co-transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) with AECS. The addition of hUCMSCs to this system enhanced the proliferation, migration, and melanin synthesis capabilities of the ECs. These findings were validated in vivo, with the hUCMSCs co-transplantation group demonstrating superior skin repigmentation efficacy in mice. Then gene interference, overexpression, and transcriptome analyses were conducted to elucidate the mechanisms underlying the Tumor Necrosis Factor Alpha-Induced Protein 2 (TNFAIP2)-Tunneling Nanotubes (TNTs) system in mediating melanin synthesis. Our findings outline a novel pathway through which hUCMSCs, via the TNFAIP2-TNT system, mediate the delivery of mitochondria to melanocytes, enhancing the function of MCs. This presents new avenues for improving the repigmentation efficacy of AECS transplantation.

Vitiligo is an autoimmune disorder characterized by the destruction of melanocytes, resulting in white skin patches that significantly affect patients' social interactions. Current clinical interventions, including immunosuppressants, phototherapy, and transplantation, aim to restore pigmentation but often fail in distal areas or long-standing cases. Bioinspired melanin-like nanoparticles (NPs), such as polydopamine (PDA) NPs, are developed as synthetic analogs of eumelanin with antioxidative and immunomodulatory properties. Here, various melanin-like NPs are compared in terms of their physical characteristics and redox activities. Based on these findings, PDA NPs modified with polyethylene glycol (PEG), termed PDA@PEG NPs, are incorporated into dissolvable microneedle (MN) patches for transdermal delivery. In a vitiligo mouse model, these patches deliver NPs into the superficial dermis, where PDA@PEG NPs serve a dual role in promoting repigmentation: (1) they offer a brown-toned concealing effect to camouflage depigmented areas and (2) they alleviate oxidative stress and reduce CD8⁺ T cell infiltration. Mechanistically, the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway is activated by PDA@PEG NPs. These findings support the potential of PDA@PEG/MN patches as a minimally invasive, multifunctional platform for accelerating repigmentation in vitiligo.

Exposure to ultraviolet (UV) radiation compromises both the aesthetic and functional properties of the skin, accelerates aging, increases the risk of skin cancer, and significantly impairs quality of life. Exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Exo) and natural compounds such as epigallocatechin gallate (EGCG) show great therapeutic potential for UV-induced skin damage. However, their efficacy is often limited by poor stability, low bioavailability, and inefficient skin penetration. In this study, we show that hUMSC-Exo and EGCG act synergistically to reduce oxidative stress and exert potent anti-inflammatory effects. By incorporating these agents into a microneedle-based delivery system, we achieved efficient transdermal co-delivery, which significantly enhanced the repair of UV-induced skin injury. The treatment markedly attenuated inflammatory responses, reduced DNA damage, and promoted tissue regeneration. These findings suggest that hUMSC-Exo/EGCG-loaded microneedles provide a simple yet effective strategy for treating UV-induced skin damage and aging, with potential applicability to a broader range of inflammatory skin conditions.

Introduction: Current research shows that there is no vitiligo quality-of-life measurement instrument suitable for Chinese patients. At present, the DLQI scale commonly used with vitiligo patients in China includes symptom dimensions or items that are not applicable to vitiligo patients. Therefore, it is necessary to develop a quality-of-life scale specific to vitiligo patients in China.Methods: In this study, the item pool was created through a comprehensive review of relevant literature, focus group discussions, and brainstorming. Two rounds of Delphi expert consultation and a semi-structured interview were conducted to modify the item pool and form the draft scale. Two rounds of questionnaire investigations were used to select items and form the final scale. The reliability, validity, and discriminative ability were evaluated based on the third round of questionnaire investigation.Results: The scale contains 3 dimensions and 25 items, and the total cumulative variance contribution rate was 64.54%. The Cronbach’s α coefficient was 0.972; the split-half reliability coefficient was 0.950, and the test–retest reliability coefficient was 0.776. The Spearman correlation coefficient with the Dermatology Life Quality Index (DLQI) was 0.650. The scores of the scale or each dimension were correlated with patient characteristics, including gender, disease course, disease stage, Body Surface Area (BSA), and white spot area.Conclusion: This study developed the Chinese Vitiligo Quality of Life Scale (CVQLS) to measure the quality of life of vitiligo patients in China. Compared to the commonly used DLQI, the CVQLS removed items related to skin disease symptoms while incorporating concerns specific to Chinese patients, such as the economic burden. The scale is thus tailored to the needs of Chinese vitiligo patients. Preliminary results indicate that the CVQLS has good reliability, validity, and discriminative ability.

Vitiligo is an autoimmune disease characterized by epidermal melanocyte destruction, with abnormal autoimmune responses and excessive oxidative stress as two cardinal mechanisms. Human umbilical mesenchymal stem cells‐derived exosomes (hUMSCs‐Exos) are regarded as promising therapeutic choice for autoimmune diseases due to potent immunosuppressive and anti‐oxidative properties, which can be potentiated under 3D cell culture condition. Nevertheless, whether exosomes derived from 3D spheroids of hUMSCs (3D‐Exos) exhibit considerable therapeutic effect on vitiligo and the underlying mechanism remain elusive. In this study, systemic administration of 3D‐Exos showed a remarkable effect in treating mice with vitiligo, as revealed by ameliorated skin depigmentation, less CD8⁺T cells infiltration, and expanded Treg cells in skin, and 3D‐Exos exerted a better effect than 2D‐Exos. Mechanistically, 3D‐Exos can prominently facilitate the expansion of Treg cells in vitiligo lesion and suppress H₂O₂‐induced melanocytes apoptosis. Forward miRNA profile analysis and molecular experiments have demonstrated that miR‐132‐3p and miR‐125b‐5p enriched in 3D‐Exos greatly contributed to these biological effects by targeting Sirt1 and Bak1 respectively. In aggregate, 3D‐Exos can efficiently ameliorate vitiligo by simultaneously potentiating Treg cells‐mediated immunosuppression and suppressing oxidative stress‐induced melanocyte damage via the delivery of miR‐132‐3p and miR‐125b‐5p. The employment of 3D‐Exos will be a promising treament for vitiligo.

Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.

Background: Observational studies suggest that ulceration is considered to be a negative prognostic factor for cutaneous melanoma. However, the impact of ulceration over different subgroups (e.g. AJCC Stage, thickness level) are controversial and its true causal effect on survival is lack of studies in the view of treating ulceration as an exposure.Objective: To explore the true causal effect of ulceration on melanoma’s survival by adopting a combination of methods to discover proper adjustment set and confirming its correctness through a variety of means.Methods: A minimal sufficient adjustment set (MSAS) was found using directed acyclic graphs (DAG) to adjust the effect of causality. Sensitivity analysis was conducted to diagnose potential confounders in addition to MSAS. Cox models were built to analyze the causality in-depth and the model was validated using a novel method. Lastly, stratified effects of ulceration were examined to illustrate its impact within subgroups.Results: Hazard ratio (HR) of ulceration after adjustment by MSAS variables was 1.99 (95% CI=1.88-2.09). The sensitivity analysis of propensity score matching and E-value both demonstrated that variables other than MSAS do not have great influence on ulceration and MSS relationship. The HR of ulceration in AJCC Stage, thickness level, invasion level and tumor extension were all monotonically decreased from 5.76 to 1.57, 4.03 to 1.78, 2.75 to 1.78 and 2.65 to 1.71 respectively.Conclusion: Ulceration in all subgroups were shown to have a significantly negative impact on MSS and its magnitude of effect was monotonically decreased as the disease progressed. The true effect of ulceration can be adjusted by MSAS and its correctness was validated through a variety of approaches.