AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed eithe...AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.展开更多
目的探讨缺氧缺血性脑病新生儿血清miR-27a、miR-17-5p、miR-181a表达水平及其临床意义。方法选取2018年3月至2024年3月石家庄市妇幼保健院收治的184例缺氧缺血性脑病新生儿为研究组,随访6个月后,根据随访结果将其分为预后良好组和预后...目的探讨缺氧缺血性脑病新生儿血清miR-27a、miR-17-5p、miR-181a表达水平及其临床意义。方法选取2018年3月至2024年3月石家庄市妇幼保健院收治的184例缺氧缺血性脑病新生儿为研究组,随访6个月后,根据随访结果将其分为预后良好组和预后不良组;另选取同期在石家庄市妇幼保健院分娩的205例健康新生儿作为对照组。采用实时荧光定量PCR(qRT-PCR)测定各组血清miR-27a、miR-17-5p、miR-181a的相对表达水平。绘制受试者工作特征(ROC)曲线分析血清miR-27a、miR-17-5p、miR-181a单独及3项联合对缺氧缺血性脑病新生儿预后不良的预测价值。采用多因素Logistic回归分析缺氧缺血性脑病新生儿预后不良的影响因素。结果与对照组相比,研究组血清miR-27a、miR-17-5p表达水平降低,miR-181a表达水平升高,差异均有统计学意义(P<0.05)。6个月随访结果显示,预后良好组有128例,预后不良组有56例;与预后良好组相比,预后不良组血清miR-27a、miR-17-5p表达水平降低,miR-181a表达水平、宫内窘迫占比、1 min Apgar评分<4分占比升高,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清miR-27a、miR-17-5p、miR-181a联合预测缺氧缺血性脑病新生儿预后不良的曲线下面积(AUC)大于miR-27a、miR-17-5p、miR-181a单独预测的AUC(Z=3.041、3.587、2.907,均P<0.05)。多因素Logistic回归分析结果显示,宫内窘迫、1 min Apgar评分及miR-181a、miR-27a、miR-17-5p表达水平均为缺氧缺血性脑病新生儿预后不良的影响因素(P<0.05)。结论缺氧缺血性脑病新生儿血清miR-27a、miR-17-5p呈低表达,miR-181a呈高表达,且均为预后不良的影响因素,三者联合检测能提高缺氧缺血新生儿预后不良的预测效能。展开更多
文摘AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.
文摘目的探讨缺氧缺血性脑病新生儿血清miR-27a、miR-17-5p、miR-181a表达水平及其临床意义。方法选取2018年3月至2024年3月石家庄市妇幼保健院收治的184例缺氧缺血性脑病新生儿为研究组,随访6个月后,根据随访结果将其分为预后良好组和预后不良组;另选取同期在石家庄市妇幼保健院分娩的205例健康新生儿作为对照组。采用实时荧光定量PCR(qRT-PCR)测定各组血清miR-27a、miR-17-5p、miR-181a的相对表达水平。绘制受试者工作特征(ROC)曲线分析血清miR-27a、miR-17-5p、miR-181a单独及3项联合对缺氧缺血性脑病新生儿预后不良的预测价值。采用多因素Logistic回归分析缺氧缺血性脑病新生儿预后不良的影响因素。结果与对照组相比,研究组血清miR-27a、miR-17-5p表达水平降低,miR-181a表达水平升高,差异均有统计学意义(P<0.05)。6个月随访结果显示,预后良好组有128例,预后不良组有56例;与预后良好组相比,预后不良组血清miR-27a、miR-17-5p表达水平降低,miR-181a表达水平、宫内窘迫占比、1 min Apgar评分<4分占比升高,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清miR-27a、miR-17-5p、miR-181a联合预测缺氧缺血性脑病新生儿预后不良的曲线下面积(AUC)大于miR-27a、miR-17-5p、miR-181a单独预测的AUC(Z=3.041、3.587、2.907,均P<0.05)。多因素Logistic回归分析结果显示,宫内窘迫、1 min Apgar评分及miR-181a、miR-27a、miR-17-5p表达水平均为缺氧缺血性脑病新生儿预后不良的影响因素(P<0.05)。结论缺氧缺血性脑病新生儿血清miR-27a、miR-17-5p呈低表达,miR-181a呈高表达,且均为预后不良的影响因素,三者联合检测能提高缺氧缺血新生儿预后不良的预测效能。
