RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤坏死因子α抑制改善子痫前期大鼠模型中的胎儿生长
英文原题：Tumor necrosis factor alpha inhibition improves fetal growth in a rat model of preeclampsia.
查看英文原题
Tumor necrosis factor alpha inhibition improves fetal growth in a rat model of preeclampsia.
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研究概要
这些结果提示，Etan-RUPP 中胎儿生长改善，且不依赖于胎盘形态或营养转运体表达，并对成年 RUPP 子代炎症产生性别特异性影响。
研究思路结论见上方概要
背景
肿瘤坏死因子α（TNF-α）在子痫前期女性中升高2倍。临床前研究表明，TNF-α阻断可降低子宫灌注压降低（RUPP）大鼠的母体血压，并减轻胎儿体重的下降。然而，该疗法对胎儿生长及潜在发病机制的获益与风险尚不清楚。因此，本研究检验了以下假说：在子痫前期RUPP模型中，与Sham对照相比，妊娠晚期使用可溶性TNF-α抑制剂依那西普（Etan）进行母体治疗可改善胎盘灌注、营养转运和形态，从而改善胎儿生长。我们进一步假设，母体Etan治疗与子代血压和炎症特征的改善相关。
方法
在妊娠第14天（GD14）进行假手术或RUPP手术，并在GD18给予溶媒或Etan（0.4 mg/kg，皮下注射）。
结果
在GD20时，RUPP组的胎儿体重（p = 0.0365）和存活率（p = 0.0002）降低；Etan-RUPP组仅胎儿体重改善（p = 0.0480）。在GD20时，RUPP组子宫动脉阻力指数（UARI）升高（p = 0.0094），但在Etan-RUPP组中减弱，表明胎盘灌注改善。RUPP组胎盘转运和形态明显受损，Etan-RUPP组未见改善。Etan-RUPP组出生体重改善（p = 0.0312），尽管雌性Etan-RUPP子代中总NK细胞增加（p = 0.0376）。成年雄性和雌性RUPP子代循环AT1-AA活性升高（p = 0.0013，p = 0.0006），但在雌性Etan-RUPP子代中减弱。
展开英文摘要原文
METHODS
Sham or RUPP surgery was performed at gestational day (GD) 14, with vehicle or Etan (0.4 mg/kg, s.c.) administered at GD18.
RESULTS
Fetal weight (p = 0.0365) and survival (p = 0.0002) were reduced in RUPP (p = 0.0365) at GD20; only fetal weight was improved in Etan-RUPP (p = 0.0480). At GD20, uterine artery resistance index (UARI) was increased in RUPP (p = 0.0094), but attenuated in Etan-RUPP, indicating improved placental perfusion. Impaired placental transport and morphology were evident in RUPP, with no improvement in Etan-RUPP. Birthweight was improved in Etan-RUPP (p = 0.0312), although total NK cells (p = 0.0376) were increased in female Etan-RUPP offspring. Circulating AT1-AA activity was elevated in adult male and female RUPP offspring (p = 0.0013, p = 0.0006), but attenuated in female Etan-RUPP offspring. DISCUSSION: These results suggest improved fetal growth in Etan-RUPP, independent of placental morphology or nutrient transporter expression, with sex-specific effects on inflammation in adult RUPP offspring.
论文信息
- 作者
- Coats LE、Campbell N、Solise D、Chamoun GM、Rawls AZ、Demesa A、Turner T、Zheng B
- 第一作者单位
- Department of Obstetrics & Gynecology, University of Mississippi Medical Center, Jackson, MS, 39216, USA; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson MS, 39216, USA.United States
- 通讯作者单位
- Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson MS, 39216, USA. Electronic address: balexander@umc.edu.United States
- 期刊
- Placenta2026 Mar 25
- 原文标识
- PubMed 41671937 · DOI 10.1016/j.placenta.2026.02.002
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