Pigment production is a unique character of melanocytes. Numerous factors are linked with melanin production, including genetics, ultraviolet radiation (UVR) and inflammation. Understanding the mechanism of melanogenesis is crucial to identify new preventive and therapeutic strategies in the treatment of melanoma. Here, we reviewed the current available literatures on the mechanisms of melanogenesis, including the signaling pathways of UVR-induced pigment production, MC1R’s central determinant roles and MITF as a master transcriptional regulator in melanogenesis. Moreover, we further highlighted the role of targeting BRAF, NRAS and MC1R in melanoma prevention and treatment. The combination therapeutics of immunotherapy and targeted kinase inhibitors are becoming the newest therapeutic option in advanced melanoma.

Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro−/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin.

Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8⁺ cells (representing CD8⁺ T cells) and CD57⁺ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA⁺ cells and GSDMB⁺ cells were predominantly expressed in immune cells, especially in CD8 ⁺ T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA⁺ merged CD8⁺ T cells (0.11%) and GSDMB⁺ merged CD57⁺ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.