Annals of dermatology最新文献

Background: Excessive growth of keratinocytes is the critical event in the etiology of psoriasis. However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear.

Objective: This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis.

Methods: We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2 in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2'-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo.

Results: We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo.

Conclusion: Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

Background: The Wnt/β-catenin signaling pathway is crucial for the development, initiation, and growth of hair follicles (HFs). The Dickkopf-related protein (DKK) gene family encodes secreted proteins modulating the Wnt/β-catenin signaling pathway. Studies have reported that DKK1 promotes the regression of HFs and serves as a pathogenic mediator in male pattern baldness. However, the role of DKK2 on human hair growth has not yet been explored.

Objective: This study investigates direct effect of DKK2 on hair growth using human dermal papilla cell (DPC) cultures and ex vivo human HF organ cultures.

Methods: To elucidate the effect of DKK2 on hair growth, we examined the effect of recombinant human DKK2 (rhDKK2) treatment on cell viability, expression of mRNA and protein related to the Wnt/β-catenin signaling pathway, and cell growth in cultured human DPCs. We also performed ex vivo organ culture of HFs with rhDKK2 and measured changes in hair shaft length for 8 days.

Results: Treatment with rhDKK2 led to a dose-dependent rise in the proliferation of human DPCs (p<0.05), reaching levels comparable to those induced by 1 μM minoxidil. Moreover, rhDKK2 increased the expression of Wnt/β-catenin target genes, phosphorylated extracellular signal-regulated kinase, and cyclin-D1; it also increased the BAX-to-Bcl-2 ratio and downregulated the bone morphogenetic protein 2 gene. In human HF organ cultures, relative to the control treatment, rhDKK2 treatment significantly increased hair shaft elongation (p<0.01).

Conclusion: Our results indicate that rhDKK2 could promote hair growth by facilitating the proliferation of human DPCs through activation of the Wnt/β-catenin signaling pathway.

Background: The need for an objective method for measuring skin hydration levels is becoming increasingly important. Various devices with different measuring principles for assessing skin hydration have been developed and are widely used.

Objective: This study aimed to investigate the reproducibility and correlation between clinical evaluation and skin hydration measurement devices that are the most widely used in the field.

Methods: A prospective comparative clinical trial was conducted on 184 healthy volunteers. Skin hydration levels were measured using the Corneometer (CM820) and hydration probe (HP: DermaLab Combo) at 3 points: the ventral forearm, the dorsal forearm, and the shin. We used the intraclass correlation coefficient (ICC) to evaluate the reproducibility and Pearson's correlation coefficient (PCC) to evaluate the correlation of each measurement. Simple linear regression was used to analyze the Corneometer and HP skin hydration value changes according to changes in xerosis severity scale (XSS) values, which were evaluated by clinicians.

Results: Both the Corneometer and HP showed significant, excellent reproducibility (ICC for Corneometer: 0.954-0.971, ICC for HP: 0.980-0.986) and significant high positive correlations (PCC: 0.708-0.737) regardless of the measurement site. Both devices showed negative regression coefficients in all measurement sites in XSS analysis, but this was not statistically significant.

Conclusion: The Corneometer and HP were both accurate and objective skin hydration measuring devices, regardless of the measurement site. Using reliable and objective devices such as the Corneometer or HP can aid in understanding an individual's skin condition and making more informed decisions for skin care.

Trial registration: Clinical Research Information Service Identifier: KCT0005146.

Dermatomyositis (DM) is a rare autoimmune connective tissue disease with characteristic skin manifestations and possible muscle involvement. Recent advances in classification system to include skin-predominant subtypes, understanding underlying pathogenic mechanisms and the relationship between clinical phenotypes and myositis-specific autoantibodies have led to development of novel therapeutic options. This corresponds with efforts to develop better outcome measures to accurately catch the patients' current disease status and treatment-induced improvements. This report will review the updates in newer treatments and outcome measures of DM, specifically from a dermatologic point of view.

Background: Radiofrequency (RF) and intense pulsed light (IPL) have been reported as efficient adjuvant treatment modalities for acne vulgaris.

Objective: We sought to evaluate the clinical efficacy and safety of a combined needle RF and vacuum IPL device for acne treatment without the use of other conventional topical or oral agents.

Methods: This randomized, split-faced study was designed to include patients with moderate to severe acne vulgaris. Comedone extraction was performed on both parts of the face prior to laser treatment. One side of the face was treated with RF and IPL in 2-week intervals, while the other side was left untreated as a control. Two independent blinded investigators evaluated the patients for improvement using clinical photographs. We also assessed for possible adverse effects.

Results: The study included 44 patients with acne vulgaris (27 men and 17 women). Their ages ranged from 19-39 years (average, 23 years). At the final 12-week follow-up visit, the acne reduction rate was 34.80% (±33.45%; range, 30.92%-19.03%) on the treated side and 13.76% (±37.58%; range, 28.26%-23.27%) in the control group compared to baseline, constituting a significant difference. The difference in reduction rate between the treated and control sides was 21.03% (±25.09%), with the treated side experiencing more significant improvement (p<0.05). In the assessment of adverse events, one patient experienced mild surrounding erythema that spontaneously improved.

Conclusion: Combined treatment of needle RF and IPL could improve acne lesions.

Background: The interest toward the association between atopic dermatitis (AD) and obesity is increasing, yet the possibility of abnormal lipid metabolism has never been investigated before.

Objective: To identify the characteristics of patients with AD who are obese and analyze the serum lipid profiles of these patients.

Methods: This observational study included 167 patients diagnosed with AD and underwent evaluations for serum lipid panels between July 2017 and October 2017. The patients' body mass index was used to determine obesity and the serum lipid panels were analyzed between patients who are obese and non-obese. Also, the disease severity and subjective symptoms were evaluated and serum total immunoglobulin E (IgE) and specific IgE levels were assessed.

Results: Of the 167 patients with AD, there were 36 obese and 131 non-obese subjects. Obese patients were found to have a significantly higher disease severity, as well as higher serum triglyceride and low-density lipoprotein-cholesterol levels and lower high-density lipoprotein-cholesterol levels, which was most pronounced in adult males. Obesity AD patients also had a significantly higher serum total IgE, itch intensity score, and number of allergens sensitized.

Conclusion: Patients with AD who are obese should be monitored for possible abnormalities in lipid metabolism. Obesity may be a factor that contributes to a higher disease severity of AD.

Background: Melasma is a common and chronic pigmentary disorder with complex pathogenesis, and the relationship between melasma and metabolic syndrome remains elusive. Thus, metabolomics might contribute to the early detection of potential metabolic abnormalities in individuals with melasma.

Objective: The present study aims to analyze changes in plasma metabolites of female melasma patients and identify disease markers as well as explore potential therapeutic targets.

Methods: Plasma samples from 20 female patients with melasma and 21 healthy female controls that were comparable in terms of age and body mass index were collected for untargeted metabolomics investigations. Ultra-high performance liquid chromatography-mass spectrometry was used to analyze metabolites in the plasma. Metabolic pathway analyses were employed to identify significantly differentially expressed metabolites in melasma patients. Receiver operating characteristic curves were constructed, and correlation analyses were performed using the modified Melasma Area and Severity Index and oxidative stress levels.

Results: In contrast to healthy subjects, melasma patients showed significant alterations in 125 plasma metabolites, including amino acids, lipids, and carbohydrate-related metabolites. KEGG pathway analysis suggested that primary pathways associated with the development of melasma include tryptophan metabolism, as well as the biosynthesis of phenylalanine, tyrosine, and tryptophan. Importantly, based on receiver operating characteristic curves and correlation analyses, several metabolites were identified as robust biomarkers for melasma.

Conclusion: Collectively, this study identified significant changes in plasma metabolites in melasma patients, providing new insights into the pathogenesis of melasma and opening novel therapeutic avenues.