Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D...Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.展开更多
目的探讨25-OH维生素D(25-OH vitamin D,25-OH-VD)对新生儿感染性肺炎(neonatal infectious pneumonia,NIP)的抗炎作用及其作用机制。方法选取2022年1月~2023年1月成都市妇女儿童中心医院收治的65例NIP患儿,根据病情严重程度,分为轻症组...目的探讨25-OH维生素D(25-OH vitamin D,25-OH-VD)对新生儿感染性肺炎(neonatal infectious pneumonia,NIP)的抗炎作用及其作用机制。方法选取2022年1月~2023年1月成都市妇女儿童中心医院收治的65例NIP患儿,根据病情严重程度,分为轻症组(n=34)和重症组(n=31),另选取同期60例健康新生儿为对照组。通过酶联免疫吸附试验(ELISA)检测血清25-OH-VD,白细胞介素-2(inteleukin-2,IL-2)、γ干扰素(interferon-γ,IFN-γ)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和IL-1β水平;蛋白免疫印迹法检测外周血单个核细胞中维生素D受体(vitamin D receptor,VDR)、细胞核转化生长因子β(transforming growth factorβ,TGF-β)/Yes相关蛋白(nucleus-Yes-associated protein,n-YAP)和细胞核转录共激活因子PDZ结合基序(nucleus-transcriptional coactivator with PDZ-binding motif,n-TAZ)通路相关蛋白表达。脂多糖(lipopolysaccharide,LPS)刺激人肺上皮细胞构建NIP体外模型,分为Control组、LPS组和LPS+VD组;CCK-8检测细胞活力;qRT-PCR检测各组细胞中细胞色素P450家族成员28B1(recombinant cytochrome P45027B1,CYP27B1)和VDR的mRNA表达;免疫细胞化学法检测各组细胞YAP阳性细胞核数;免疫荧光检测各组细胞YAP/TAZ复合物核转位;蛋白免疫印迹法检测各组细胞炎性因子相关蛋白表达。结果与对照组相比,轻症组和重症组患儿血清中IL-2(1.91±0.18μg/L,2.63±0.27μg/L vs 1.05±0.12μg/L),IFN-γ(1.73±0.13μg/L,2.18±0.19μg/L vs 1.03±0.07μg/L),TNF-α(1.79±0.08μg/L,2.38±0.13μg/L vs 0.97±0.04μg/L)和IL-1β(2.18±0.07μg/L,2.59±0.11μg/L vs 0.96±0.02μg/L)含量以及TGF-β(1.67±0.21,2.43±0.42 vs 1.02±0.04),n-YAP(2.08±0.11,4.23±0.37 vs 0.99±0.02)和n-TAZ(2.47±0.42,4.21±0.58 vs 1.03±0.05)蛋白表达逐渐升高,25-OH-VD(12.57±2.21μg/L,7.85±2.03μg/L vs 16.76±1.02μg/L)含量和VDR(0.73±0.09,0.51±0.06 vs 1.03±0.08)蛋白表达逐渐降低,差异具有统计学意义(F=18.983~56.782,均P<0.001)。细胞实验结果显示,与Control组相比,LPS组细胞存活率在12h(76.23%±0.73%vs 116.72%±2.14%),24 h(57.23%±0.94%vs 125.76%±1.67%)和48 h(41.23%±0.56%vs 138.56%±1.35%)时显著降低(t=10.342,26.562,37.821);YAP阳性细胞数(47.35±3.47个vs 12.46±1.34个)和YAP/TAZ复合物核转位率(2.56%±0.32%vs 1.01%±0.06%)升高(t=46.362,26.921);IL-2(2.03±0.09 vs 1.03±0.08),IFN-γ(2.07±0.21 vs 1.02±0.04),TNF-α(2.18±0.11 vs 0.99±0.02)和IL-1β(3.17±0.42 vs 1.03±0.05)的蛋白表达水平升高(t=28.341,26.713,31.235,47.823),差异具有统计学意义(均P<0.001),而两组间CYP27B1和VDR mRNA表达差异无统计学意义(t=0.872,0.786,均P>0.05)。与LPS组比较,LPS+VD组在12 h(85.23%±0.36%),24 h(79.82%±0.63%),48 h(76.28%±0.72%)的细胞存活率和CYP27B1(4.42±0.14),VDR mRNA(5.13±0.56)表达升高,YAP阳性细胞核数(24.41±3.23个)和YAP/TAZ复合物核转位率(1.47%±0.26%)降低,IL-2(1.21±0.06),IFN-γ(1.13±0.42),TNF-α(1.03±0.37)和IL-1β(1.61±0.58)蛋白表达降低,差异具有统计学意义(t=7.263,19.892,23.145,27.872,26.982,14.762,13.623,18.273,25.314,27.873,22.134,均P<0.01)。结论血清25-OH-VD水平与NIP严重程度相关,外源性给予VD补充可通过调控TGF-β介导的YAP/TAZ核转位机制发挥抗炎作用,减轻NIP损伤。展开更多
基金funded by the Nactional Natural Science Foundation of China(81872618)。
文摘Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.
文摘目的探讨25-OH维生素D(25-OH vitamin D,25-OH-VD)对新生儿感染性肺炎(neonatal infectious pneumonia,NIP)的抗炎作用及其作用机制。方法选取2022年1月~2023年1月成都市妇女儿童中心医院收治的65例NIP患儿,根据病情严重程度,分为轻症组(n=34)和重症组(n=31),另选取同期60例健康新生儿为对照组。通过酶联免疫吸附试验(ELISA)检测血清25-OH-VD,白细胞介素-2(inteleukin-2,IL-2)、γ干扰素(interferon-γ,IFN-γ)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和IL-1β水平;蛋白免疫印迹法检测外周血单个核细胞中维生素D受体(vitamin D receptor,VDR)、细胞核转化生长因子β(transforming growth factorβ,TGF-β)/Yes相关蛋白(nucleus-Yes-associated protein,n-YAP)和细胞核转录共激活因子PDZ结合基序(nucleus-transcriptional coactivator with PDZ-binding motif,n-TAZ)通路相关蛋白表达。脂多糖(lipopolysaccharide,LPS)刺激人肺上皮细胞构建NIP体外模型,分为Control组、LPS组和LPS+VD组;CCK-8检测细胞活力;qRT-PCR检测各组细胞中细胞色素P450家族成员28B1(recombinant cytochrome P45027B1,CYP27B1)和VDR的mRNA表达;免疫细胞化学法检测各组细胞YAP阳性细胞核数;免疫荧光检测各组细胞YAP/TAZ复合物核转位;蛋白免疫印迹法检测各组细胞炎性因子相关蛋白表达。结果与对照组相比,轻症组和重症组患儿血清中IL-2(1.91±0.18μg/L,2.63±0.27μg/L vs 1.05±0.12μg/L),IFN-γ(1.73±0.13μg/L,2.18±0.19μg/L vs 1.03±0.07μg/L),TNF-α(1.79±0.08μg/L,2.38±0.13μg/L vs 0.97±0.04μg/L)和IL-1β(2.18±0.07μg/L,2.59±0.11μg/L vs 0.96±0.02μg/L)含量以及TGF-β(1.67±0.21,2.43±0.42 vs 1.02±0.04),n-YAP(2.08±0.11,4.23±0.37 vs 0.99±0.02)和n-TAZ(2.47±0.42,4.21±0.58 vs 1.03±0.05)蛋白表达逐渐升高,25-OH-VD(12.57±2.21μg/L,7.85±2.03μg/L vs 16.76±1.02μg/L)含量和VDR(0.73±0.09,0.51±0.06 vs 1.03±0.08)蛋白表达逐渐降低,差异具有统计学意义(F=18.983~56.782,均P<0.001)。细胞实验结果显示,与Control组相比,LPS组细胞存活率在12h(76.23%±0.73%vs 116.72%±2.14%),24 h(57.23%±0.94%vs 125.76%±1.67%)和48 h(41.23%±0.56%vs 138.56%±1.35%)时显著降低(t=10.342,26.562,37.821);YAP阳性细胞数(47.35±3.47个vs 12.46±1.34个)和YAP/TAZ复合物核转位率(2.56%±0.32%vs 1.01%±0.06%)升高(t=46.362,26.921);IL-2(2.03±0.09 vs 1.03±0.08),IFN-γ(2.07±0.21 vs 1.02±0.04),TNF-α(2.18±0.11 vs 0.99±0.02)和IL-1β(3.17±0.42 vs 1.03±0.05)的蛋白表达水平升高(t=28.341,26.713,31.235,47.823),差异具有统计学意义(均P<0.001),而两组间CYP27B1和VDR mRNA表达差异无统计学意义(t=0.872,0.786,均P>0.05)。与LPS组比较,LPS+VD组在12 h(85.23%±0.36%),24 h(79.82%±0.63%),48 h(76.28%±0.72%)的细胞存活率和CYP27B1(4.42±0.14),VDR mRNA(5.13±0.56)表达升高,YAP阳性细胞核数(24.41±3.23个)和YAP/TAZ复合物核转位率(1.47%±0.26%)降低,IL-2(1.21±0.06),IFN-γ(1.13±0.42),TNF-α(1.03±0.37)和IL-1β(1.61±0.58)蛋白表达降低,差异具有统计学意义(t=7.263,19.892,23.145,27.872,26.982,14.762,13.623,18.273,25.314,27.873,22.134,均P<0.01)。结论血清25-OH-VD水平与NIP严重程度相关,外源性给予VD补充可通过调控TGF-β介导的YAP/TAZ核转位机制发挥抗炎作用,减轻NIP损伤。
