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Infected wounds can result in complex clinical complications and delayed healing, presenting a significant global public health challenge. This study explored the effects of topical application of two probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis BB‐12, on the microenvironment of infected wounds and their impact on wound healing. LGG and BB‐12 were applied separately and topically on the Staphylococcus aureus (S. aureus)‐infected skin wounds of the rat model on a daily basis. Both probiotics significantly accelerated wound healing, demonstrated by enhanced granulation tissue formation and increased collagen deposition, with BB‐12 showing superior efficacy. LGG and BB‐12 both effectively inhibited neutrophil infiltration and decreased the expression of pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). Notably, BB‐12 markedly reduced IL‐6 levels, while LGG significantly lowered TNF‐α, transforming growth factor‐β (TGF‐β) and vascular endothelial growth factor (VEGF). Additionally, both probiotics promoted macrophage polarization towards the anti‐inflammatory M2 phenotype. Microbiota analysis revealed that LGG and BB‐12 significantly decreased the abundance of pathogenic bacteria (e.g. Staphylococcus and Proteus) and increased the proportion of beneficial bacteria (e.g. Corynebacterium). Particularly, BB‐12 was more effective in reducing Staphylococcus abundance, whereas LGG excelled in promoting Corynebacterium growth. These findings suggest the ability of LGG and BB‐12 to modulate the wound microenvironment, enhance wound healing and provide valuable insights for the management of infected wounds.
Infected wounds can result in complex clinical complications and delayed healing, presenting a significant global public health challenge. This study explored the effects of topical application of two probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis BB‐12, on the microenvironment of infected wounds and their impact on wound healing. LGG and BB‐12 were applied separately and topically on the Staphylococcus aureus (S. aureus)‐infected skin wounds of the rat model on a daily basis. Both probiotics significantly accelerated wound healing, demonstrated by enhanced granulation tissue formation and increased collagen deposition, with BB‐12 showing superior efficacy. LGG and BB‐12 both effectively inhibited neutrophil infiltration and decreased the expression of pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). Notably, BB‐12 markedly reduced IL‐6 levels, while LGG significantly lowered TNF‐α, transforming growth factor‐β (TGF‐β) and vascular endothelial growth factor (VEGF). Additionally, both probiotics promoted macrophage polarization towards the anti‐inflammatory M2 phenotype. Microbiota analysis revealed that LGG and BB‐12 significantly decreased the abundance of pathogenic bacteria (e.g. Staphylococcus and Proteus) and increased the proportion of beneficial bacteria (e.g. Corynebacterium). Particularly, BB‐12 was more effective in reducing Staphylococcus abundance, whereas LGG excelled in promoting Corynebacterium growth. These findings suggest the ability of LGG and BB‐12 to modulate the wound microenvironment, enhance wound healing and provide valuable insights for the management of infected wounds.
BackgroundAnoikis disrupts the normal apoptotic process in cells, leading to abnormal proliferation and migration, thereby promoting tumor formation and development. However, the role of anoikis in bladder urothelial carcinoma (BLCA) still requires further exploration.MethodsAnoikis-related genes (ARGs) were retrieved from the GeneCards and Harmonizome databases to distinguish various subtypes of BLCA and develop a predictive model for BLCA. The immune microenvironment and enrichment pathways between various subtypes were also analyzed using consensus clustering. Potential medications were screened by utilizing drug sensitivity analysis. In vitro and vivo, the character of the independent prognostic gene in BLCA was confirmed through cell studies and mouse xenograft models.ResultsOne hundred thirty differentially expressed genes (DEGs) were identified, and nine of them were chosen to construct predictive models that can accurately forecast the prognosis of BLCA patients. K = 2 was correctly identified as the optimal clustering type for BLCA, showing prominent differences in survival rates between the two subgroups. The immune-related functional studies manifested that the two subtypes’ immune cell expressions differed. It was verified that RAC3 is an independent prognostic gene for BLCA. RAC3 shows high expression levels in BLCA, as indicated by its consistent mRNA and protein levels across different gene expressions. The functional verification results of RAC3 in BLCA showed that silencing RAC3 can significantly inhibit BLCA cell proliferation, colony formation, and migration. RAC3 knockdown inhibited the growth and migration of BLCA in vivo. SB505124 exhibited a significant inhibitory effect on the proliferation of BLCA cells.ConclusionBased on the predictive model developed in this study, BLCA patients’ prognoses can be accurately predicted. SB505124 could become an important drug in the treatment of BLCA patients. RAC3 is essential in prognosis, immune microenvironment, and malignant behavior of BLCA in vitro and in vivo. It will also offer the potential for personalized treatment for BLCA patients and generate new research avenues for clinical investigators.
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