Journal of dermatological science最新文献

Background: Macrophages are key regulators of tissue repair, with M2-polarized subsets promoting anti-inflammatory, pro-regenerative functions. Decoy Receptor 3 (DcR3), a soluble TNF receptor superfamily member, modulates macrophage polarization, but its role in cutaneous regeneration remains unclear.

Objective: To elucidate the immunomodulatory role of DcR3 in macrophage polarization and evaluate its therapeutic potential in skin wound repair and hair follicle regeneration.

Methods: We employed a combination of in vitro macrophage polarization assays with in vivo models, including delayed wound healing and mechanical stretch-induced hair regeneration, to evaluate DcR3-mediated immunoregulation. Transgenic mice with macrophage-specific DcR3 overexpression were employed to investigate the physiological function of endogenous DcR3.

Results: DcR3 accelerated wound closure and dampened pro-inflammatory gene expression in LPS-treated wounds. While physiological hair cycling remained unchanged in DcR3-transgenic mice, mechanical stimulation elicited enhanced anagen induction. In vitro, DcR3 attenuated M1 polarization while amplifying IL-4-induced M2 gene expression, thereby promoting macrophage plasticity. Adoptive transfer of DcR3-reprogrammed macrophages improved both wound healing and hair regrowth by reshaping the wound microenvironment, reducing iNOS2⁺ M1-like and increasing CD206⁺ M2-like macrophage, while enriching the transitional iNOS2⁺CD206⁺ macrophage population.

Conclusion: DcR3 facilitates macrophage reprogramming toward reparative phenotypes and enhances regenerative responses in skin and hair follicles, establishing DcR3 as a promising immunoregulatory target for chronic wound management and alopecia treatment.

Background: Low-temperature plasma (LTP) is an essential technology in engineering that originated in materials science. Its applications have recently been expanded to biology, where it is referred to as plasma biology. LTP and LTP-activated solutions are now used for wound healing and sterilization. One emerging field is cancer treatment.

Objective: To evaluate the effectiveness of LTP-activated Ringer's lactate solution (PAL) against malignant melanoma.

Methods: Cells of the A375 malignant melanoma line were subcutaneously injected into nude mice. PAL was administered three times weekly, and tumor growth was measured. Cell viability was measured using MTS assay in vitro experiments. Whole transcriptome sequencing and qRT-PCR were conducted to reveal differentially expressed mRNAs. To detect DNA double-strand breaks, immunofluorescence of γ-H2AX foci was performed. Mitochondrial membrane potential and apoptosis were detected by JC-1 probe and caspase-3/7 detection reagents, respectively.

Results: The PAL exhibited an anti-cancer effect in the A375 xenograft mouse model. The PAL also showed in vitro cytotoxicity for a melanoma cell line. Comprehensive RNA expression analysis revealed the downregulation of multiple heat shock proteins (HSPs), especially HSPA1A, HSPA1B, HSPA6, HSPA7 and DNAJB1. HSP insufficiency induced lower mitochondrial membrane potential. The mode of cell death for the melanoma cells was apoptosis.

Conclusion: PAL is suggested as a promising new therapeutic agent for malignant melanoma.

Background: Alopecia is a prevalent clinical condition with currently limited therapeutic options. Salvianolic acid B (Sal B) has demonstrated promising regenerative properties across various disease models. However, its potential role in the treatment of alopecia and the underlying mechanisms remain largely unexplored.

Objective: To elucidate the role and mechanisms of Sal B in hair regeneration, we evaluated its effects on hair loss model in vivo and in vitro, and integrated multi-omics analysis.

Methods: We performed reverse molecular docking screening using the LRP6 receptor (PDB: 7NAM) to identify Sal B as a top candidate. Network pharmacology and molecular docking were used to predict target genes and binding affinity. Sal B was treated with cultured DPCs and hair follicles to investigate its effects on DPC proliferation. In vivo efficacy was evaluated in murine alopecia and AGA. Integrated multi-omics analysis, complemented by Western blot and PCR, was employed to elucidate the key signaling pathways.

Results: Sal B bound strongly to LRP6 and promoted DPC proliferation, migration, and stemness. It enhanced hair shaft elongation in vitro and stimulated hair regeneration in mice, outperforming minoxidil in AGA models. Multi-omics analyses revealed enrichment in mTOR signaling, matrix metalloproteinases (MMPs), and MAPK pathways. Sal B activated mTORC2/Akt signaling, upregulated RICTOR, downregulated DEPTOR, and enhanced phosphorylation of Akt and GSK-3β, leading to β-catenin stabilization. It also increased expression of MMP9, MMP3, MMP1, and activated ERK and p38.

Conclusion: Sal B promotes hair regeneration through dual activation of the Wnt/β-catenin and mTORC2/Akt pathways, and upregulation of MMPs and MAPKs.

Background: Melanoma is recognized as the most aggressive type of skin cancer, characterized by its high mortality rates and significant therapeutic challenges.

Objective: The primary aim of this research is to analyze cellular heterogeneity in SKCM through single-cell RNA sequencing (scRNA-seq) and construct a neddylation-related prognostic model.

Methods: The scRNA-seq and bulk data of Skin Cutaneous Melanoma (SKCM) samples were obtained from Gene Expression Omnibus and Cancer Genome Atlas Program databases. The nonnegative matrix factorization clustering algorithm was employed to stratify malignant cells into different neddylation cell subtypes in SKCM.

Results: The scRNA-seq analysis classified 31,894 high-quality cells into eight major cell types, revealing significant cellular distribution patterns within the TME. We observed that neddylation activity was significantly elevated in SKCM tissues compared to normal counterparts. Based on the expression profile of prognostic NRGs, the malignant cells were stratified into four neddylation cell subtypes in SKCM. A neddylation-related prognostic signature (NRPS) was established based on marker genes of neddylation-C3 cell subtype. The low-risk group activated immune-related signaling pathways, while the high-risk group activated various cancer-related pathways. Notably, the low-risk group exhibited better overall survival, higher immune cell infiltration, and response rates to immunotherapy compared to the high-risk group.

Conclusion: This investigation emphasizes the crucial function of NRGs in the prognosis of SKCM, while also underscoring the importance of understanding the TME and its cellular heterogeneity. The distinct cellular composition and functional attributes within the TME highlight the potential for immunotherapy responses that can be stratified by risk.