PDF(Pubmed)
Abstract：
UNASSIGNED: Diabetic foot ulcer (DFU) impairs the quality of life of diabetic patients and overburdens healthcare systems and society. It is crucial to comprehend the pathophysiology of DFU and develop effective treatment strategies. The aim of this study was to to evaluate the therapeutic potential of Lactobacillus Plantarum (LP) on wound healing in DFU and to explore the underlying mechanisms.
UNASSIGNED: To investigate the effects of LP on wound healing, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs) and used to assess cell viability, migration, and pyroptosis using CCK-8, cell scratch, and flow cytometry. The levels of IL-1β and IL-18 were measured by ELISA. The expression of NLRP3, caspase-1 p20, and GSDMD-N was detected by Western blot. Additionally, NLRP3 inhibitor MCC950 was used to treat a diabetic rat model established by streptozotocin (STZ). Pearson correlation analysis was performed to analyze the relationship between LP and NLRP3, IL-1β, IL-18 in ulcer tissue.
UNASSIGNED: Our data mechanistically demonstrate that AGEs activate the NLRP3/Caspase-1/GSDMD pathway, leading to an increase in the levels of IL-1β and IL-18 and ultimately promoting cell pyroptosis. Furthermore, we identified that LP inhibits the effects of AGEs by downregulating NLRP3 inflammasome activity. LP facilitated wound healing in diabetic rats and resulted in decreased protein levels of NLRP3 and its downstream target caspase-1 p20. Finally, we observed a negative correlation between LP and NLRP3, IL-1β, IL-18 in diabetic foot skin tissue.
UNASSIGNED: Our findings uncovered a novel role of LP in diabetic foot wound healing via regulation of the NLRP3 inflammasome, suggesting this link as a therapeutic target. In future research, it would be valuable to explore the signaling cascades involved in LP-mediated inhibition of NLRP3 inflammasome activation.
UNASSIGNED: To investigate the effects of LP on wound healing, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs) and used to assess cell viability, migration, and pyroptosis using CCK-8, cell scratch, and flow cytometry. The levels of IL-1β and IL-18 were measured by ELISA. The expression of NLRP3, caspase-1 p20, and GSDMD-N was detected by Western blot. Additionally, NLRP3 inhibitor MCC950 was used to treat a diabetic rat model established by streptozotocin (STZ). Pearson correlation analysis was performed to analyze the relationship between LP and NLRP3, IL-1β, IL-18 in ulcer tissue.
UNASSIGNED: Our data mechanistically demonstrate that AGEs activate the NLRP3/Caspase-1/GSDMD pathway, leading to an increase in the levels of IL-1β and IL-18 and ultimately promoting cell pyroptosis. Furthermore, we identified that LP inhibits the effects of AGEs by downregulating NLRP3 inflammasome activity. LP facilitated wound healing in diabetic rats and resulted in decreased protein levels of NLRP3 and its downstream target caspase-1 p20. Finally, we observed a negative correlation between LP and NLRP3, IL-1β, IL-18 in diabetic foot skin tissue.
UNASSIGNED: Our findings uncovered a novel role of LP in diabetic foot wound healing via regulation of the NLRP3 inflammasome, suggesting this link as a therapeutic target. In future research, it would be valuable to explore the signaling cascades involved in LP-mediated inhibition of NLRP3 inflammasome activation.
摘要：
■糖尿病足溃疡（DFU）会损害糖尿病患者的生活质量，并使医疗保健系统和社会负担过重。了解DFU的病理生理学并制定有效的治疗策略至关重要。这项研究的目的是评估植物乳杆菌（LP）对DFU伤口愈合的治疗潜力，并探讨其潜在机制。
■为了研究LP对伤口愈合的影响，人脐静脉内皮细胞（HUVECs）用晚期糖基化终产物（AGEs）处理，用于评估细胞活力，迁移,使用CCK-8，细胞划痕，和流式细胞术。ELISA法检测IL-1β和IL-18水平。Westernblot检测NLRP3、caspase-1p20和GSDMD-N的表达。此外,NLRP3抑制剂MCC950用于治疗链脲佐菌素（STZ）建立的糖尿病大鼠模型。采用Pearson相关分析分析LP与NLRP3、IL-1β、溃疡组织中的IL-18。
■我们的数据从机制上证明AGEs激活了NLRP3/Caspase-1/GSDMD通路，导致IL-1β和IL-18水平增加并最终促进细胞焦亡。此外，我们发现LP通过下调NLRP3炎性体活性来抑制AGEs的作用.LP促进糖尿病大鼠的伤口愈合，并导致NLRP3及其下游靶标caspase-1p20的蛋白质水平降低。最后,我们观察到LP和NLRP3，IL-1β，糖尿病足皮肤组织中的IL-18。
■我们的发现揭示了LP通过调节NLRP3炎性体在糖尿病足伤口愈合中的新作用，表明这种联系是一种治疗靶点。在未来的研究中,探索LP介导的NLRP3炎性体激活抑制中涉及的信号级联反应将是有价值的。
■为了研究LP对伤口愈合的影响，人脐静脉内皮细胞（HUVECs）用晚期糖基化终产物（AGEs）处理，用于评估细胞活力，迁移,使用CCK-8，细胞划痕，和流式细胞术。ELISA法检测IL-1β和IL-18水平。Westernblot检测NLRP3、caspase-1p20和GSDMD-N的表达。此外,NLRP3抑制剂MCC950用于治疗链脲佐菌素（STZ）建立的糖尿病大鼠模型。采用Pearson相关分析分析LP与NLRP3、IL-1β、溃疡组织中的IL-18。
■我们的数据从机制上证明AGEs激活了NLRP3/Caspase-1/GSDMD通路，导致IL-1β和IL-18水平增加并最终促进细胞焦亡。此外，我们发现LP通过下调NLRP3炎性体活性来抑制AGEs的作用.LP促进糖尿病大鼠的伤口愈合，并导致NLRP3及其下游靶标caspase-1p20的蛋白质水平降低。最后,我们观察到LP和NLRP3，IL-1β，糖尿病足皮肤组织中的IL-18。
■我们的发现揭示了LP通过调节NLRP3炎性体在糖尿病足伤口愈合中的新作用，表明这种联系是一种治疗靶点。在未来的研究中,探索LP介导的NLRP3炎性体激活抑制中涉及的信号级联反应将是有价值的。
