Network pharmacology-based identification for therapeutic mechanisms of Dangguikushen pill in acne vulgaris.

The Dangguikushen (DGKS) pill is a proprietary traditional Chinese medicine that has shown superior efficacy in the treatment of acne vulgaris for many years. A network pharmacology-based analysis was performed to explore the potential anti-acne compounds, core therapeutic targets, and the main pathways, involved in the DGKS pill bioactivity. The matching results between the predicted targets of the DGKS pill and the well-known targets of acne vulgaris were collected, followed by network establishment using protein-protein interaction (PPI) data. Cytoscape was utilized to analyze the network and screen the core targets. Furthermore, the Database for Annotation, Visualization and Integrated Discovery (DAVID), and ClueGO were used for the enrichment analysis of the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathways and Gene Ontology biological processes (GO-BP). Finally, the "compound-target-pathway" network was constructed. This approach identified 19 active compounds, 46 therapeutic targets, and 12 core therapeutic targets of the DGKS pill. The biological processes were primarily related to reactive oxygen species (ROS) metabolic process, gland morphogenesis, and female gonad development. The DGKS pill was significantly associated with eight pathways including the PI3K-Akt, TNF, NF-kappa B, and p53 signaling pathways. DGKS pill might have a synergistic effect on the inhibition of excessive sebaceous lipogenesis and sebocyte differentiation, and likewise, anti-inflammatory effects via the different signaling pathways (PI3K-Akt, TNF, NF-kappa B, and p53).

UVA1 vs. narrowband UVB phototherapy in the treatment of palmoplantar pustulosis: a pilot randomized controlled study.

UVA1 phototherapy, a new therapeutic approach, has recently been shown good efficacy in the treatment of palmoplantar pustulosis (PPP). The purpose of this study was to compare the efficacy of UVA1 and narrowband UVB (NB-UVB) therapy in the treatment of PPP. Patients with PPP were randomly assigned to either UVA1 or NB-UVB therapy according to a left-right randomization table. Both treatments were performed three times weekly for up to 30 sessions. Clinical evaluation was based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) score. Totally 64 patients completed the study. Both UVA1 and NB-UVB therapy showed a statistically significant reduction of PPPASI score compared with the baseline value at the end of the treatment period (P < 0.05). There was a significantly greater mean reduction of PPPASI score in the UVA1 treated group when compared to the NB-UVB treated patients at 30 sessions (6.0 ± 2.4 vs. 4.4 ± 1.4, P < 0.05). No phototoxic reaction or bullous changes were observed in either group. Both NB-UVB and UVA1 phototherapy of PPP resulted in significant improvement. UVA1 phototherapy was more effective than NB-UVB irradiation in the treatment of PPP.

UVA1 phototherapy in the treatment of palmoplantar pustulosis: a pilot prospective study.

Palmoplantar pustulosis (PPP) is recalcitrant to traditional topical and systemic therapies. Ultraviolet A1 (UVA1) phototherapy, a new therapeutic approach, has recently been shown good efficacy in the treatment of PPP. The purpose of this study was to evaluate the efficacy and safety of UVA1 therapy for the treatment of PPP. Patients with PPP were treated with UVA1 irradiation three times a week for up to 30 sessions and had a 3-month follow-up visit. UVA1 therapy was conducted with a fixed dose (80 J/cm2). Clinical evaluation was based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) score. Totally, 62 patients completed the study. The mean PPPASI score decreased from a baseline value of 9.4 ± 2.8 to a value of 4.9 ± 2.4 at 15 sessions, 1.7 ± 1.9 at 30 sessions, and 2.0 ± 2.1 at follow-up visit. A reduction of 75 % in the PPPASI score was observed in 4 (6.5 %) patients at 15 sessions and 45 (72.6 %) patients at 30 sessions. The adverse effects were limited including burning sensation, pruritus, and hyperpigmentation. UVA1 is an effective therapy for PPP with mild side effects.

Unequal relevance between different subtypes of fingernail psoriasis and psoriatic arthritis.

Nail disease in psoriasis has been found to be associated with psoriatic arthritis (PsA); however, which subtype of nail disease holds greater relevance to PsA remains unclear. This study was performed to explore the associations between three subtypes of fingernail disease (pitting, onycholysis, and hyperkeratosis) and PsA among patients with psoriasis. Patients with psoriasis attending five dermatology clinics in Shanghai between January 2020 and May 2021 were examined for skin, joint, and fingernail changes. Multivariate logistic regression analyses were utilized to test the strength of associations between subtypes of fingernail disease and PsA. The receiver operator characteristic (ROC) curve with area under curve (AUC) was used to evaluate their accuracies in diagnosing PsA. Sensitivity and specificity were also calculated. Of 1985 patients with psoriasis included, 228 (11.5%) patients were diagnosed with PsA, and the remaining patients were cutaneous-only psoriasis (PsC). One-hundred and fifty-seven (68.9%) patients with PsA and 748 (42.6%) patients with PsC had fingernail disease. Adjusted models showed that onycholysis and hyperkeratosis were the only type of fingernail disease independently associated with PsA. This association was further confirmed by the forward conditional stepwise regression model (OR, 95% CI for onycholysis: 2.34, 1.79 to 4.27, p < 0.01; for hyperkeratosis: 1.62, 1.12 to 2.66, p = 0.037). ROC analysis showed that, compared to pitting and hyperkeratosis, onycholysis had higher AUC (0.630) and sensitivity (52.6%). The psoriatic fingernail onycholysis and hyperkeratosis hold greater relevance to PsA than pitting. Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis. Key Points • Psoriatic fingernail onycholysis and hyperkeratosis, rather than pitting, are significantly associated with PsA • Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis.

Assessment of four screening tools and retrieval of key questions to detect undiagnosed psoriatic arthritis in Chinese patients with psoriasis: A multicenter study.

Several screening tools have been developed to facilitate early diagnosis of psoriatic arthritis (PsA); however, their performance varied greatly across different studies. In this study, we validated and compared the performance of four screening tools in detecting undiagnosed PsA Chinese patients with psoriasis, and determined the key questions and their weights. The four screening tools were the Early Arthritis for Psoriatic Patients (EARP) questionnaire, Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire, Psoriasis and Arthritis Screening Questionnaire (PASQ), and Psoriasis Epidemiology Screening Tool (PEST). The receiver-operator curve (ROC) with area under curve (AUC) was used to determine sensitivity, specificity, and accuracy. Least absolute shrinkage and selection operator and logistic regression were utilized to retrieve key questions, and a nomogram was utilized to visualize their weights. Of 482 psoriasis patients from dermatology clinics, 77 were newly diagnosed with PsA. Another 68 patients with newly diagnosed PsA from rheumatology clinics were incorporated in the analysis. ROC analysis indicated that the optimal cut-off values for EARP, PASE, PASQ, and PEST were 3, 40, 7, and 3, with corresponding sensitivities of 91.4%, 88.6%, 86.2%, and 88.5%, and specificities of 88.6%, 75.2%, 80.2%, and 83.6%, respectively. The AUC of EARP (0.925) was higher than those of PASE (0.885), PASQ (0.905), and PEST (0.827). However, none of them were sufficiently sensitive to identify pure axial PsA (sensitivities of EARP, PASQ, and PASE were 25.0%, 36.8%, and 42.1%, respectively). Twelve key questions were retrieved from these four tools to establish a nomogram with a high discrimination (C-index = 0.993) and a good calibration (mean absolute error = 0.014). In conclusion, to screen undiagnosed PsA, EARP has slightly better balanced sensitivity and specificity, and higher accuracy. The retrieval of key questions and nomogram signify the necessity of attributing different scores to differently weighted questions when developing a new screening tool to make it function more efficiently.

Drug Survival Outcomes Associated with the Real-World Use of Ixekizumab, Secukinumab, Guselkumab, and Adalimumab for the Treatment of Plaque Psoriasis in China: A 52-Week Single-Center Retrospective Study.

Background: Data pertaining to biologic agents used for treating psoriasis in real-world settings are lacking at present. To compare drug survival at 52 weeks for a range of biologics used to treat psoriasis under real-world conditions. Methods: This was a retrospective, single-center, observational study of a cohort of patients diagnosed with plaque psoriasis treated using ixekizumab, secukinumab, guselkumab, or adalimumab between January 2020 and December 2021. Baseline demographic characteristics, duration of psoriasis, and prior biological treatments for all patients were recorded. Drug survival rates were analyzed in different patient groups using Kaplan-Meier curves and Log rank tests. Results: In total, this study included 386 plaque psoriasis patients, of whom 70, 175, 36, and 105 were, respectively, treated using ixekizumab, secukinumab, guselkumab, and adalimumab. Over a 52-week period, the overall cumulative drug survival rates for ixekizumab, secukinumab, guselkumab, and adalimumab were 67.1%, 63.0%, 72.2%, and 37.1%, respectively. Lack of efficacy was the primary cause of discontinuation for these biologic therapies, followed by economic burden and adverse event incidence. Conclusion: These results suggest that guselkumab exhibited superior drug survival, drug survival outcomes for ixekizumab and secukinumab were comparable, and significantly better than those of adalimumab in China. Preventing a loss of drug efficacy represents a primary approach to improving biologic drug survival in psoriasis patients.

Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial-mesenchymal transition in melanoma cells.

Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metastatic melanoma tissues than in normal skin, cutaneous squamous cell carcinoma or basal cell carcinoma. Melanoma cells overexpressing UBE3C frequently exhibited a mesenchymal phenotype, including reduced expression of the epithelial marker E-cadherin and expression of the mesenchymal marker vimentin. Knockdown of UBE3C expression in melanoma cells significantly suppressed melanoma growth and progression. Furthermore, silencing UBE3C led to increased E-cadherin expression and decreased vimentin and Snail1 expression. Thus UBE3C promotes melanoma progression, possibly by inducing epithelial-mesenchymal transition in melanoma cells. Inhibiting UBE3C activity may suppress melanoma invasion and metastasis and may represent a targeted therapeutic approach.