UV exposure leads to skin damage, thus inducing skin aging. The aims of this study were to explore the differences in tRNA-derived small RNAs (tsRNAs) expression in the Human dermal fibroblasts (HDF cells) photoaging cell model and to explore the biological functions of tsRNA in skin photoaging. In this study, we found that in both photoaging cell models and the skin of photoaging mice, the 5'-tiRNA-His-GTG expression levels were significantly elevated. In HDF cells, overexpression of 5'-tiRNA-His-GTG induces cellular senescence. Inhibition of 5'-tiRNA-His-GTG attenuates UVB-induced cellular senescence in the photoaging cell model. Intradermal injection of Adeno-associated virus 9-5'-tiRNA-His-GTG -Inhibition ameliorates UVB-induced skin photoaging in nude mice. We confirmed that 5'-tiRNA-His-GTG targeted nuclear pore proteins 98, which further activated the JNK signaling pathway and induced cell senescence. Targeting 5'-tiRNA-His-GTG may provide a novel therapeutic option for ameliorating skin photoaging.

Various types of drug-induced vitiligo-like depigmentation have been reported in recent years. Commonly implicated drugs include immune checkpoint inhibitors, targeted drugs, monoclonal antibodies, immunomodulators, chemotherapy drugs, and imiquimod. Unlike the mechanism of vitiligo, the mechanism of drug-induced vitiligo-like depigmentation is not clear, and it has some different characteristics. We herein summarize the vitiligo-like depigmentation induced by different drugs, which will help dermatologists to further understand its pathogenesis and clinical features.

tRNA-derived small RNAs (tsRNAs), a class of non-coding RNAs (ncRNAs), have garnered increasing research interest for their potential roles in various biological processes. Among these, 5'tiRNA-Glu-TTC has been implicated in aging, but its role in skin photoaging remains elusive. This study aimed to elucidate the impact of 5'tiRNA-Glu-TTC on skin photoaging. RT-qPCR analysis revealed that 5'tiRNA-Glu-TTC expression increased in human dermal fibroblasts (HDFs), human skin tissues, and mouse skin tissues following UVB irradiation. In HDFs, transfection of a 5'tiRNA-Glu-TTC mimic induced photoaging phenotypes, while its inhibitor alleviated UVB-induced photoaging. This study found that 5'tiRNA-Glu-TTC participates in photoaging through binding to TRPV3. Overexpression of TRPV3 rescued the photoaging effects induced by the 5'tiRNA-Glu-TTC mimic. Furthermore, 5'tiRNA-Glu-TTC influences photoaging also by activating the PI3K/AKT signaling pathway, an effect that was reversed by TRPV3 overexpression. In vivo studies in nude mice showed that intradermal injection of 5'tiRNA-Glu-TTC adeno-associated virus alleviated UVB-induced skin aging phenotypes, including epidermal thickening, dermal collagen reduction, and increased transepidermal water loss (TEWL). Collectively, our findings demonstrate that 5'tiRNA-Glu-TTC mediates photoaging by targeting TRPV3 and activating the PI3K/AKT pathway.

Psoriasis is a chronic, inflammatory skin disorder driven by dysregulated keratinocyte-immune interactions and oxidative stress. To address limitations of conventional therapies, we engineered a sulfated bacterial cellulose/chitosan hydrogel that integrates intrinsic bioactivity with controlled methotrexate delivery (MTX-SBC/CS Gel). Sulfonation introduced sulfonic groups, conferring potent ROS-scavenging activity while optimizing drug compatibility and release kinetics. Chitosan enabled self-healing and bioadhesion through hydrogen-bonding networks. Molecular simulations and experiments revealed how sulfonic groups modulate drug-polymer interactions. In imiquimod-induced psoriatic models, MTX-SBC/CS Gel exhibited therapeutic efficacy comparable to that of the clinical standard betamethasone, with SBC alone showing beneficial effects; both accelerated epidermal normalization, and cytokine suppression. Transcriptomics identified SBC’s multimodal mechanism: downregulation of IL-23/Th17 axis components, inhibition of keratinocyte hyperproliferation, and restoration of redox homeostasis via HSP90α-mediated pathways. The synergistic integration of sulfonation-enabled ROS scavenging, and optimized MTX release kinetics establishes this engineered hydrogel as a promising platform for the management of dermatoses.

Previous studies have proven that 308-nm light-emitting diode(308-nm LED)and 308-nm excimer lamp(308-nm MEL) are effective in treating vitiligo, but there is a lack of comparison of their efficacy for facial lesions. To evaluate and contrast the treatment success rates of 308-nm LED versus 308-nm excimer lamp in managing facial lesions among patients suffering from stable non-segmental vitiligo. The enrolled 119 patients with 145 lesions were randomly assigned to receive 308-nm LED or 308-nm MEL for two months. Two independent investigators graded repigmentation at the end of the 2-month treatment period. There were 76 lesions in the 308-nm LED group and 69 in the 308-nm MEL group. After 1 month, the average repigmentation grade of the 308-nm LED group was 1.34, with an efficacy rate of 11.84

BACKGROUND:Actinic keratoses (AK) may progress into squamous cell carcinoma. Many combination therapies were used to improve the clearance rate. However, there are limited studies on the efficacy and safety of lesion-directed Liquid nitrogen cryotherapy combined with field-directed photodynamic therapy (PDT). OBJECTIVE:This study is aimed to determine the efficacy and safety of Liquid nitrogen cryotherapy combined with PDT in Chinese patients with actinic keratosis. METHODS:A total of 61 patients with AK were selected at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2018 and August 2023. They were randomly divided into PDT plus Liquid nitrogen cryotherapy group (LN-PDT) and control PDT group (C-PDT) with 30 patients and 31 patients, respectively. 27 patients in the LN-PDT group and 28 patients in the C-PDT group completed the clinical sessions. Efficacy, adverse effects, and cosmetic outcomes were recorded and compared between the two groups. RESULTS:3 months after the final treatment, the clearance rates for total AK lesions were 97.4 % (449/461) in the LN-PDT group and 93.4 % (456/488) in the C-PDT group (P < 0.05). For grade I AK lesions, the clearance rates were 99.2 % (234/237) for the LN-PDT group and 98.3 % (237/241) for the C-PDT group (P >0.05). For grade II lesions, the clearance rates were 97.5 % (156/160) for the LN-PDT group and 91.9 % (172/186) for the CPDT group (P < 0.05). For grade III lesions, the clearance rates of the LN-PDT and C-PDT groups were 87.5 % (58/64) and 78.7 % (47/61), respectively (P < 0.05). The two groups had no significant differences in pain, erythema, edema, hyperpigmentation and scarring. Cosmetic outcomes mainly were excellent or good in both groups with no significant difference. CONCLUSION:Liquid nitrogen cryotherapy combined with PDT showed higher efficacy on grade II and grade III AK lesions than PDT alone. The two groups have similar adverse effects and cosmetic outcomes.

BackgroundPsoriasis is a chronic, inflammatory skin disease. MicroRNAs (miRNAs) are an abundant class of non-coding RNA molecules. Recent studies have shown that multiple miRNAs are abnormally expressed in patients with psoriasis. The upregulation of miR-374a-5p has been associated with psoriasis severity. However, the specific role of miR-374a-5p in the pathogenesis of psoriasis remain unclear.MethodsqRT-PCR was employed to validate the expression of miR-374a-5p in psoriatic lesions and in a psoriasis-like cell model constructed using a mixture of M5 (IL-17A, IL-22, OSM, IL-1α, and TNF-α). HaCaT cells were transfected with miR-374a-5p mimic/inhibitor, and assays including EdU, CCK-8, and flow cytometry were conducted to evaluate the effect of miR-374a-5p on cell proliferation. The expression of inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α was verified by qRT-PCR. Bioinformatics analysis and dual-luciferase reporter gene assay were performed to detect the downstream target genes and upstream transcription factors of miR-374a-5p, followed by validation of their expression through qRT-PCR and Western blotting. A psoriasis-like mouse model was established using imiquimod cream topical application. The psoriasis area and severity index scoring, hematoxylin-eosin histology staining, and Ki67 immunohistochemistry were employed to validate the effect of miR-374a-5p on the psoriatic inflammation phenotype after intradermal injection of miR-374a-5p agomir/NC. Additionally, the expression of pathway-related molecules and inflammatory factors such as IL-1β, IL-17a, and TNF-α was verified by immunohistochemistry.ResultsUpregulation of miR-374a-5p was observed in psoriatic lesions and the psoriasis-like cell model. In vitro experiments demonstrated that miR-374a-5p not only promoted the proliferation of HaCaT cells but also upregulated the expression of inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α. Furthermore, miR-374a-5p promoted skin inflammation and epidermal thickening in the Imiquimod-induced psoriasis-like mouse model. Mechanistic studies revealed that miR-374a-5p led to downregulation of WIF1, thereby activating the Wnt5a/NF-κB signaling pathway. The transcription factor p65 encoded by RELA, as a subunit of NF-κB, further upregulated the expression of miR-374a-5p upon activation. This positive feedback loop promoted keratinocyte proliferation and abnormal inflammation, thereby facilitating the development of psoriasis.ConclusionOur findings elucidate the role of miR-374a-5p upregulation in the pathogenesis of psoriasis through inhibition of WIF1 and activation of the Wnt5a/NF-κB pathway, providing new potential therapeutic targets for psoriasis.

BACKGROUND:In previous studies, the 308-nm light-emitting diode (LED) has been proven safe and effective for treating vitiligo. However, direct comparisons between the 308-nm LED and 308-nm excimer lamp (308-nm MEL) for the treatment of vitiligo are lacking.OBJECTIVE:To compare the efficacy of the 308-nm LED and 308-nm MEL for treating nonsegmental stable vitiligo.PATIENTS AND METHODS:This randomized controlled trial was conducted between January 2018 and August 2023. Enrolled patients were randomly assigned to either the 308-nm LED or the 308-nm MEL groups, both receiving 16 treatment sessions. Adverse events that occurred during the treatment were documented.RESULTS:In total, 269 stable vitiligo patches from 174 patients completed the study. A total of 131 lesions were included in the 308-nm LED group, and 138 lesions were included in the 308-nm MEL group. After 16 treatment sessions, 38.17% of the vitiligo patches in the 308-nm LED group achieved repigmentation of at least 50% versus 38.41% in the 308-nm MEL group. The two devices exhibited similar results in terms of efficacy for a repigmentation of at least 50% (p = .968). The incidence of adverse effects with the two phototherapy devices was comparable (p = .522).CONCLUSIONS:Treatment of vitiligo with the 308-nm LED had a similar efficacy rate to the 308-nm MEL, and the incidence of adverse effects was comparable between the two devices.

BackgroundCombination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor.ObjectiveTo assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris.MethodsThis was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris.ResultsA total of 1617 patients were enrolled. At week 12, patients in the adapalene-clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (- 66.85%), compared with adapalene alone (- 50.82%) or clindamycin gel alone (- 57.61%). The difference in the least square means of the adapalene-clindamycin gel group and adapalene group, or clindamycin gel group was - 16.08% (95% CI - 19.95% to - 12.21%) and - 9.38% (95% CI - 13.25% to - 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene-clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups.ConclusionAdapalene 0.1%-clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris.Trial RegistrationClinicalTrials.gov identifier NCT03615768.

BackgroundMany studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence.MethodsOur analysis utilized 15 genome-wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two-sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p-values using the Benjamini-Hochberg method.ResultsOur study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed-up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris.ConclusionOur findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed-up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris.

Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1

DNA damage resulting from UV irradiation on the skin has been extensively documented in numerous studies. In our prior investigations, we demonstrated that UVB-induced DNA breakage from keratinocytes can activate the cGAS-STING pathway in macrophages. The cGAS-STING signaling pathway serves as the principal effector for detecting and responding to abnormal double-stranded DNA in the cytoplasm. Expanding on our previous findings, we have further validated that STING knockout significantly diminishes UVB-induced skin damage, emphasizing the critical role of cGAS-STING activation in this context. Salvianolic acid A, a principal active constituent of Salvia miltiorrhiza Burge, has been extensively studied for its therapeutic effects in conditions such as coronary heart disease, angina pectoris, and diabetic peripheral neuropathy. However, its effect on cGAS-STING pathway and its ability to alleviate skin damage have not been previously reported. In a co-culture system, supernatant from UVB-treated keratinocytes induced IRF3 activation in macrophages, and this activation was inhibited by salvianolic acid A. Our investigation, employing photodamage and photoaging models, establishes that salvianolic acid A effectively mitigates UV-induced epidermal thickening and collagen degeneration. Treatment with salvianolic acid A significantly reduced skin damage, epidermal thickness increase, and keratinocyte hyperproliferation compared to the untreated photo-damage and photoaging model groups. In summary, salvianolic acid A emerges as a promising candidate for preventing UV-induced skin damage by inhibiting cGAS-STING activation. This research enhances our understanding of the intricate mechanisms underlying skin photodamage and provides a potential avenue for the development of therapeutic interventions.

Psoriasis is a chronic inflammatory dermatosis with an unclear pathogenesis. Mast cells (MCs) can serve as a bridge between innate and adaptive immunity and are involved in the regulation of the inflammatory state and immune homeostasis in diseases. MCs constitutively express interleukin-33 receptor T1/ST2 (IL-33R). IL-33 is a potent MCs activator that is actively secreted by keratinocytes in psoriasis. However, the regulatory role of MCs in psoriasis remains uncertain. Therefore, we hypothesised that IL-33 could promote MC activation to regulate psoriasis development. We performed experiments on wild-type (WT) and MC-deficient (Kit Wsh/Wsh) mice, established psoriasis-like mouse models using imiquimod (IMQ), and performed RNA sequencing and transcriptomic analysis of skin lesions. Exogenous administration was performed using recombinant IL-33. Validation and evaluation were performed using PSI scoring, immunofluorescence, immunohistochemistry, and qPCR. We observed an upregulation in the number and activation of MCs in patients with psoriasis and in IMQ-induced psoriasis-like dermatitis. Deficiency of MCs ameliorates IMQ-induced psoriatic dermatitis at an early stage. IL-33 is increased and co-localized with MCs in the dermis of psoriasis-like lesions using immunofluorescence. Compared to WT mice, IMQ-induced KitWsh/Wsh mice demonstrated a delayed response to exogenous IL-33. MCs are activated by IL-33 in the early stages of psoriasis and exacerbate psoriasis-associated skin inflammation. The regulation of MC homeostasis may be a potential therapeutic strategy for psoriasis.

The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) plays an oncogenic role in multiple cancers due to its high expression. However, the expression and associated regulatory mechanisms of PVT1 in cutaneous squamous cell carcinoma (cSCC) remain unclear. Our results revealed that PVT1 was highly upregulated in cSCC tissues and cSCC cell lines. To determine the functional role of PVT1 in cSCC, we constructed a stable knockdown cell model of PVT1 in the A431 and COLO16 cell lines using a lentiviral approach. Xenograft tumor experiments of nude mice in vivo, and colony formation, CCK-8, and EdU assays in vitro demonstrated that knockdown of PVT1 could widely suppress cell proliferation in vivo and in vitro. In addition, PVT1 knockdown induced cell cycle arrest and promoted apoptosis, as detected by flow cytometry analysis. Wound healing and transwell assays revealed that PVT1 knockdown significantly inhibited the migration and invasion of CSCC cell lines. To gain insight into the tumorigenic mechanism and explore the potential target molecules of PVT1, we employed label-free quantitative proteomic analysis. The GO, KEGG enrichment, and protein-protein interaction (PPI) networks suggested that 4E-binding protein 1 (4EBP1) is the possible downstream target effector of PVT1, which was validated by western blot analysis. PVT1 silencing markedly decreased 4EBP1 protein expression levels and directly bound 4EBP1 in the cytoplasm of cSCC cells. 4EBP1 overexpression counteracted the effects of PVT1 knockdown on tumorigenesis in cSCC cells, including cell proliferation, apoptosis, migration, and invasion. Our findings provide strong evidence that PVT1 is an oncogene which plays a role in tumorigenesis of cSCC, that PVT1 may interact with 4EBP1 in the cytoplasm as an underlying mechanism in cSCC carcinogenesis, and that PVT1 combined with 4EBP1 may serve as a potential new therapeutic target for cSCC.

Aim: To identify DNA methylation and transcription biomarkers in the psoriatic epidermis. Materials & methods: Gene transcription and DNA methylation datasets of psoriatic epidermal tissue were obtained from the Gene Expression Omnibus. Machine learning algorithm analysis and weighted gene coexpression network analysis were carried out to screen hub genes. Results: Differentially methylated and expressed genes were identified in the psoriatic epidermis. Six hub genes were selected - GZMB, CRIP1, S100A12, ISG15, CRABP2 and VNN1 - whose transcript levels showed a significant correlation with Psoriasis Area and Severity Index scores and immune infiltration. Conclusion: Psoriatic epidermis is primarily in a hypermethylated status. Epidermis-specific hub differentially methylated and expressed genes are potential biomarkers to help judge the condition of psoriasis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that promotes the degradation of low-density lipoprotein receptors. It is involved in hyperlipidemia as well as other diseases, such as cancer and skin inflammation. However, the detailed mechanism for PCSK9 on ultraviolet B (UVB)-induced skin lesions was not clear. Thus, the role and possible action mechanism of PCSK9 in UVB-induced skin damage in mice were studied here using siRNA and a small molecule inhibitor (SBC110736) against PCSK9. Immunohistochemical staining revealed a significant increase in PCSK9 expression after UVB exposure, indicating the possible role of PCSK9 in UVB damage. Skin damage, increase in epidermal thickness, and keratinocyte hyperproliferation were significantly alleviated after treatment with SBC110736 or siRNA duplexes, compared with that in the UVB model group. Notably, UVB exposure triggered DNA damage in keratinocytes, whereas substantial interferon regulatory factor 3 (IRF3) activation was observed in macrophages. Pharmacologic inhibition of STING or cGAS knockout significantly reduced UVB-induced damage. In the co-culture system, supernatant from UVB-treated keratinocyte induced IRF3 activation in macrophages. This activation was inhibited with SBC110736 and by PCSK9 knockdown. Collectively, our findings reveal that PCSK9 plays a critical role in the crosstalk between damaged keratinocytes and STING activation in macrophages. The interruption of this crosstalk by PCSK9 inhibition may be a potential therapeutic strategy for UVB-induced skin damage.

Objective:To observe the efficacy and adverse reactions of fractional radiofrequency (FRF) in the treatment of facial acne scars.Methods:Fifty-seven patients with facial acne depressed scars were enrolled with the nature of Dreno scars as the diagnostic criteria. They were treated with lattice radiofrequency. The treatment heads were arranged in a matrix with a treatment area of 1.2 cm ×1.2 cm, an energy density of 80-100 mJ/pin, and an interval of five-seven once a week. And they were followed up and evaluated for the clinical efficacy and adverse reactions 6 months after the last treatment. Scoring was carried out according to the ECCA weight scores, and the efficacy judged according to complete improvement, significant improvement, moderate improvement, and mild improvement.Results:After 3 times of fractional radiofrequency treatment of 57 patients, the effective rate was 44 cases, accounting for 77.2%; the ECCA weight scores before and after treatment were 65.9±25.0 and 47.7±20.2, respectively; the difference was statistically significant ( t=13.92, P<0.001); At the same time of improvement, 32 cases of patients' complexion, fineness of pores, and skin elasticity had been improved to varying degrees, and patient satisfaction was high. Adverse reactions were mainly mild burning sensation, erythema and edema, and some patients had pale yellow exudate, etc, which could be relieved in 5-7 days. Conclusions:Fractional radiofrequency treatment of facial acne scars is safe and effective, with short recovery period, few adverse reactions and high patient satisfaction.

Objective:To compare efficacy and safety of 308-nm SQ light-emitting diode (LED) light versus 308-nm excimer light in the treatment of facial vitiligo.Methods:Patients with stable facial vitiligo were retrospectively collected from Department of Physical Therapy, Hospital of Dermatology, Chinese Academy of Medical Sciences from June 2018 to June 2020, who received treatment with 308-nm SQ LED light (LED group) or 308-nm excimer light (excimer light group). The treatment was performed once or twice a week, and patients who had received more than 8 sessions of treatment were included in the analysis of efficacy and safety. Statistical analysis was carried out by using chi-square test.Results:Totally, 68 patients with 90 lesions were enrolled into the LED group, including 36 males and 32 females, aged 25.01 ± 13.37 years; 20 patients with 28 lesions were enrolled into the excimer light group, including 13 males and 7 females, aged 27.15 ± 14.30 years. After 8 and 16 sessions of treatment, there was no significant difference in the response rate between the LED group (23.33%, 46.67%, respectively) and excimer light group (14.29%, 46.43%, χ2 = 1.05, < 0.001, respectively, both P > 0.05). During the treatment, 36 (52.94%) patients in the LED group developed persistent erythema, 17 (85%) in the excimer light group developed persistent erythema or blisters. The incidence of adverse reactions was significantly lower in the LED group than in the excimer light group ( χ2 = 16.43, P < 0.001) . Conclusion:Compared with the 308-nm excimer light, the 308-nm SQ LED light showed similar effect but higher safety for the treatment of facial vitiligo.