Necrotizing enterocolitis (NEC) is an acute intestinal condition accounting for severe mortality and morbidity in preterm infants. This study aimed to identify the possible roles of let-7d-5p in neonatal rats with NEC. The differentially expressed genes (DEGs) related to NEC were initially screened in silico. After establishment of NEC rat models, the measurement of the expression of let-7d-5p, galectin-3 (LGALS3), toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) as well as proinflammatory cytokines (TNF-α, IL-1b and IL-6) was conducted. The interaction between let-7d-5p and LGALS3 or Argonaute2 (AGO2) was identified. Gain- and loss-function approaches were then performed in an attempt to investigate the regulatory roles of let-7d-5p and LGALS3 in inflammation and cell apoptosis in NEC neonatal rats. Let-7d-5p was poorly expressed, while LGALS3, TLR4 and NF-κB were highly expressed in the intestinal tissues of NEC rats. Over-expression of let-7d-5p resulted in decreased levels of proinflammatory factors in the intestinal tissues of NEC rats. Through sequential experimentation, let-7d-5p was identified to target LGALS3 and bind to AGO2. In addition, LGALS3 silencing or LPS treatment blocked the TLR4/NF-κB signaling pathway, thereby suppressing intestinal epithelial cell apoptosis and inflammation in NEC. Collectively, let-7d-5p might exercise its inhibitory properties in the inflammatory response and intestinal epithelial cell apoptosis in NEC neonatal rats via inactivation of the LGALS3-dependent TLR4/NF-κB signaling pathway.

中文翻译：

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Let-7d-5p通过LGALS3介导的TLR4 /NF-κB信号通路抑制新生大鼠坏死性小肠结肠炎的炎症反应。

坏死性小肠结肠炎（NEC）是一种急性肠道疾病，占早产儿严重的死亡率和发病率。这项研究旨在确定let-7d-5p在NEC新生大鼠中的可能作用。最初在计算机上筛选了与NEC相关的差异表达基因（DEG）。建立NEC大鼠模型后，测量let-7d-5p，galectin-3（LGALS3），toll​​样受体4（TLR4）和核因子κB（NF-κB）以及促炎细胞因子的表达（进行TNF-α，IL-1b和IL-6）。鉴定了let-7d-5p与LGALS3或Argonaute2（AGO2）之间的相互作用。然后进行增益和丧失功能的方法，以试图研究let-7d-5p和LGALS3在NEC新生大鼠炎症和细胞凋亡中的调节作用。Let-7d-5p表达不佳，而LGALS3，TLR4和NF-κB在NEC大鼠肠组织中高表达。let-7d-5p的过度表达导致NEC大鼠肠道组织中促炎因子水平降低。通过顺序实验，let-7d-5p被鉴定为靶向LGALS3并与AGO2结合。此外，LGALS3沉默或LPS处理可阻断TLR4 /NF-κB信号通路，从而抑制NEC肠上皮细胞凋亡和炎症。总的来说，let-7d-5p可能通过灭活LGALS3依赖的TLR4 /NF-κB信号通路来抑制NEC新生大鼠的炎症反应和肠道上皮细胞凋亡。let-7d-5p的过度表达导致NEC大鼠肠道组织中促炎因子水平降低。通过顺序实验，let-7d-5p被鉴定为靶向LGALS3并与AGO2结合。此外，LGALS3沉默或LPS处理可阻断TLR4 /NF-κB信号通路，从而抑制NEC肠上皮细胞凋亡和炎症。总的来说，let-7d-5p可能通过灭活LGALS3依赖的TLR4 /NF-κB信号通路来抑制NEC新生大鼠的炎症反应和肠道上皮细胞凋亡。let-7d-5p的过度表达导致NEC大鼠肠道组织中促炎因子水平降低。通过顺序实验，let-7d-5p被鉴定为靶向LGALS3并与AGO2结合。此外，LGALS3沉默或LPS处理可阻断TLR4 /NF-κB信号通路，从而抑制NEC肠上皮细胞凋亡和炎症。总的来说，let-7d-5p可能通过灭活LGALS3依赖的TLR4 /NF-κB信号通路来抑制NEC新生大鼠的炎症反应和肠道上皮细胞凋亡。LGALS3沉默或LPS处理可阻断TLR4 /NF-κB信号通路，从而抑制NEC肠上皮细胞凋亡和炎症。总的来说，let-7d-5p可能通过灭活LGALS3依赖的TLR4 /NF-κB信号通路来抑制NEC新生大鼠的炎症反应和肠道上皮细胞凋亡。LGALS3沉默或LPS处理可阻断TLR4 /NF-κB信号通路，从而抑制NEC肠上皮细胞凋亡和炎症。总的来说，let-7d-5p可能通过灭活LGALS3依赖的TLR4 /NF-κB信号通路来抑制NEC新生大鼠的炎症反应和肠道上皮细胞凋亡。