0.5-5% Supramolecular Salicylic Acid Hydrogel is Safe for Long-Term Topical Application and Improves the Expression of Genes Related to Skin Barrier Homeostasis in Mice Models.

Background: As a keratolytic, salicylic acid (SA) can be topically applied in various formulations and doses in dermatology. Supramolecular SA hydrogel, a new SA formulation with higher bioavailability, is developed and commercially available nowadays. However, there still remain concerns that the long-term and continual application of SA at low concentrations may jeopardize the cutaneous barrier properties. Aim of the Study: To reveal the long-term effects of 0.5-5% supramolecular SA hydrogel on the skin barrier in normal mice models. Materials and Methods: The 0.5%, 1%, 2%, and 5% supramolecular SA hydrogel or hydrogel vehicle without SA was applied to mice's shaved dorsal skin once per day respectively. Tissue samples of the dorsal skin were harvested on day 14 and 28 of the serial application of SA for histopathological observation and transcriptomic analysis. Results: Following topical supramolecular SA hydrogel therapy with various concentrations of SA (0.5%, 1%, 2%, and 5%) for 14 days and 28 days, there were no obvious macroscopic signs of impaired cutaneous health and no inflammatory or degenerative abnormalities were observed in histological results. Additionally, the transcriptomic analysis revealed that on day 14, SA dramatically altered the expression of genes related to the extracellular matrix structural constituent. And on day 28, SA regulated gene expression profiles of keratinization, cornified envelope, and lipid metabolism remarkably. Furthermore, the expression of skin barrier related genes was significantly elevated after the application of SA based on RNA-seq results, and this is likely to be associated with the PPAR signaling pathway according to the enrichment analysis. Conclusion: Our findings demonstrated that the sustained topical administration of the 0.5-5% supramolecular SA hydrogel for up to 28 days did no harm to normal murine skin and upregulated the expression of genes related to the epidermal barrier.

RNA sequencing and metabolic analysis of imiquimod-induced psoriasis-like mice with chronic restrain stress.

AIM: Psoriasis is one of the most common dermatological disorders, characterized by increased epidermal hyperplasia and immune cell infiltration. Psychological stress has been reported to contribute to the severity, aggravation, and relapse of psoriasis. However, the exact mechanism involved in psychological stress's impact on psoriasis is still unclear. We aim to investigate the role of psychological stress in psoriasis from a transcriptomic and metabolomic perspective. MAIN METHOD: We developed a chronic restrain stress (CRS)-imiquimod (IMQ)-induced psoriasis-like mouse model and performed a comprehensive comparative transcriptomic and metabolic analysis with control mice, CRS-treated mice, and IMQ-treated mice to investigate how psychological stress affects psoriasis. KEY FINDING: We found that CRS-IMQ-induced psoriasis-like mice showed significant exacerbation of psoriasis-like skin inflammation compared with mice treated with IMQ only. Mice of the CRS + IMQ group showed increased expression of keratinocyte proliferation and differentiation genes, differential regulation of cytokines, and promotion of linoleic acid metabolism. Correlation analysis of differentially expressed genes in the CRS-IMQ-induced psoriasis-like mice and human psoriasis datasets compared with respective controls revealed 96 overlapping genes of which 30 genes showed consistent induced or repressed expression in all human and mouse datasets. SIGNIFICANCE: Our study provides new insights into the effects of psychological stress on psoriasis pathogenesis and the mechanisms involved, which provides clues for development of therapeutics or biomarkers.

γ-Aminobutyric acid promotes the inhibition of hair growth induced by chronic restraint stress.

Stress plays a critical role in hair loss, although the underlying mechanisms are largely unknown. γ-aminobutyric acid (GABA) has been reported to be associated with stress; however, whether it affects stress-induced hair growth inhibition is unclear. This study aimed to investigate the potential roles and mechanisms of action of GABA in chronic restraint stress (CRS)-induced hair growth inhibition. We performed RNA-seq analysis and found that differentially expressed genes (DEGs) associated with neuroactive ligand-receptor interaction, including genes related to GABA receptors, significantly changed after mice were treated with CRS. Targeted metabolomics analysis and enzyme-linked immunosorbent assay (ELISA) also showed that GABA levels in back skin tissues and serum significantly elevated in the CRS group. Notably, CRS-induced hair growth inhibition got aggravated by GABA and alleviated through GABAA antagonists, such as picrotoxin and ginkgolide A. RNA sequencing analysis revealed that DEGs related to the cell cycle, DNA replication, purine metabolism, and pyrimidine metabolism pathways were significantly downregulated in dermal papilla (DP) cells after GABA treatment. Moreover, ginkgolide A, a GABAA antagonist extracted from the leaves of Ginkgo biloba, promoted the cell cycle of DP cells. Therefore, the present study demonstrated that the increase in GABA could promote CRS-induced hair growth inhibition by downregulating the cell cycle of DP cells and suggested that ginkgolide A may be a promising therapeutic drug for hair loss.

Dermoscopy Features of Cutaneous Warts.

BACKGROUND: Cutaneous warts are benign epithelial skin lesions, caused by human papilloma virus (HPV). These warts can affect any part of the body, and the clinical presentation of cutaneous warts is highly variable, making it difficult to diagnose. Dermoscopy is a relatively new, non-invasive, diagnostic tool, which can assist in the identification of different types of skin lesions. PURPOSE: The purpose of this research article is to determine the effectiveness of dermoscopy in discerning the most common characteristics of cutaneous warts, in order to provide sufficient information on characteristic features of cutaneous warts, which may aid in differentiating cutaneous warts from other similar skin lesions. PATIENTS AND METHODS: A total of 104 patients diagnosed with warts were included in our study. Each individual case had one of the four different types of warts: common warts (26 cases), palmer warts (27 cases), plantar warts (25 cases), flat warts (26 cases). RESULTS: In this study, we found that a percentage of cutaneous warts appear clinically nonclassical, overlapping with other lesions. A 42% (11 cases) of common warts were clinically nonclassical, and all of these cases presented with papillomatous growth. Other presentations were dotted, linear vessels, hairpin-like vessels and bleeding spots. All palmar wart cases were classical, while 8% (2 cases) of plantar warts were clinically nonclassical. The dermoscopic presentations were papillomatous growth, bleeding spots, dotted and linear vessels, structureless yellowish-gray appearance. Flat wart consisted of 11.5% (3 cases) with nonclassical clinical presentation. The dermoscopic presentation includes dotted and linear vessels, bleeding spots. Red, whitish (pale) and red-gray backgrounds. CONCLUSION: Dermoscopy can improve the accuracy of diagnosing different types of clinically nonclassical cutaneous warts, as well as help in distinguishing them from other similar skin lesions.

Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells.

Our study explored the tumor-suppressive effect of curcumin on cervical cancer cells. Cervical cancer is one of the most common cancers among women worldwide. Acquired resistance to chemotherapeutics and toxicity of such drugs has undermined the effectiveness of cervical cancer treatments. Therefore, the identification of novel chemotherapeutics is key to improving the survival of patients with cervical cancer. Curcumin has been shown to have various bioactivities, including antioxidant and antitumor effects; however, its effect on cervical cancer remains elusive. Here, we used the SiHa human cervical cancer cell line to test various concentrations of curcumin on the proliferation and apoptosis of cervical cancer cells. The involvement of autophagy and reactive oxygen species (ROS) in these effects were also tested by using specific autophagy inhibitors and ROS scavengers. Our results showed that curcumin induced ROS accumulation, apoptosis, autophagy, cell cycle arrest, and cellular senescence accompanied by upregulation of p53 and p21 proteins in SiHa cells.