ABSTRACT
Background: Removal of the eschar has gradually become a consensus on treatments of deep dermal necrosis after skin trauma in recent years, whereas exaggerated scar contracture and tissue proliferation developed during healing have received little attention. Here, the authors investigated the effects of eschar on excessive wound healing of small dermal damage and focused on the role M2 macrophages played, hoping to offer a theoretical basis to improve patients' cosmetic satisfaction. Methods: A mouse dorsal wound model (nâ =â 12) was established by electric heating pads heating for 20 seconds on each side of the spine, and the left side was the preserved group. Macrophage numbers, expression of wound-healing-associated proteins, and inflammatory cytokine levels were assessed at different time points by immunohistochemistry and quantitative real-time polymerase chain reaction. A co-culture system of M2 macrophages and myofibroblasts was created in vitro. Immunohistochemistry, real-time polymerase chain reaction, and Western blot were performed to evaluate the proliferation, migration, and protein expression of myofibroblasts. Results: Preserving eschar inhibited contraction-associated proteins (α-smooth muscle actin and vimentin) and collagen expression, inflammatory cytokine (IL-1ß, IL-10, TFN-α, and IL-4) expression, and M2 macrophage infiltration. Mechanistically, M2 macrophages potentially contributed to excessive wound healing by promoting myofibroblasts proliferation, migration, and production of contraction-associated proteins. Conclusion: Eschar preservation in wounds could reduce inflammation and negatively modulate myofibroblasts by inhibiting M2 macrophage polarization and infiltration, preventing excessive wound contraction and collagen deposition.
ABSTRACT
Background: Prostate cancer (PCa) is a malignant tumor in males, with a majority of the cases advancing to metastatic castration resistance. Metastasis is the leading cause of mortality in PCa. The traditional early detection and prediction approaches cannot differentiate between the different stages of PCa. Therefore, new biomarkers are necessary for early detection and clear differentiation of PCa stages to provide precise therapeutic intervention. Methods: The objective of the study was to find significant differences in genes and combine the three GEO datasets with TCGA-PRAD datasets (DEG). Weighted gene coexpression network analysis (WGCNA) determined the gene set and PCa clinical feature correlation module utilizing the TGGA-PRAD clinical feature data. The correlation module genes were rescreened using the biological information analysis tools, with the three hub genes (TOP2A, NCAPG, and BUB1B) for proper verification. Finally, internal (TCGA) and external (GSE32571, GSE70770) validation datasets were used to validate and predict the value of last hub genes. Results: The hub gene was abnormally upregulated in PCa samples during verification. The expression of each gene was favorably connected with the Gleason score and TN tumor grade in clinical samples but negatively correlated with the overall survival rate. The expression of these genes was linked to CD8 naive cells and macrophages, among other cells. Antitumor immune cells like NK and NKT were favorably and adversely correlated with infiltrating cells, respectively. Simultaneously, the GSCV and GSEA indicated that the hub gene is connected with cell proliferation, death, and androgen receptor, among other signaling pathways. Therefore, these genes could influence the incidence and progression of PCa by participating in or modulating various signaling pathways. Furthermore, using the online tool of CMap, we examined the individual medications for Hughes and determined that tipifarnib could be useful for the clinical therapy of PCa. Conclusion: TOP2A, NCAPG, and BUB1B are important genes intimately linked to the clinical prognosis of PCa and can be employed as reliable biomarkers for early diagnosis and prognosis. Moreover, these genes can provide a theoretical basis for precision differentiation and treatment of PCa.
